Genes & Diseases

About the Journal

Genes & Diseases is an international journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch.

Aims and Scopes

Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis will be placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.

Open access journal

This journal is a peer reviewed, subsidized open access journal where Chongqing Medical University pays the OA fee. Authors do not have to pay any open access publication fee.
Peer review under the responsibility of Chongqing Medical University.

Access Rights

All articles published open access will be immediately and permanently free for everyone to read, download, copy and distribute.

User Rights

Permitted third party reuse is defined by the following user license:

Creative Commons Attribution-NonCommercial-NoDerivs (CC BY-NC-ND):

Allows users to copy and distribute the Article, provided this is not done for commercial purposes and further does not permit distribution of the Article if it is changed or edited in any way, and provided the user gives appropriate credit (with a link to the formal publication through the relevant DOI), provides a link to the license, and that the licensor is not represented as endorsing the use made of the work. The full details of the license are available at https://creativecommons.org/licenses/by-nc-nd/4.0/.
Note: If you need to comply with your funding body policy, you can apply for the CC BY license after your manuscript is accepted for publication.

Author Rights

For open access publishing, this journal uses an exclusive licensing agreement. Authors will transfer copyright to Chongqing Medical University, but will have the right to share their article in the same way permitted to third parties under the relevant user license, as well as certain scholarly usage rights.

Publishing Schedule

This journal is published quarterly; March, June, September, and December.

Learn More about:

• Publishing open access with Elsevier
• Open access license policy
• Copyright
• Policies

Editor-in-Chief

• Tong-Chuan He, MD, PhD

  • The University of Chicago Medical Center Molecular Oncology Laboratory, Chicago, United States of America

• Ailong Huang

  • Chongqing Medical University, Chongqing, China

Deputy Editor-in-Chief

• John Wang, PhD

  • Case Western Reserve University School of Medicine, Cleveland, United States of America

• Xiaodong Zhao, MD, PhD

  • Chongqing Medical University, Chongqing, China

Executive Managing Editor

• Ping Luo

  • Chongqing Medical University, Chongqing, China

Assistant Managing Editors

• Qiushan Tang

  • Chongqing Medical University, Chongqing, China

• Huijie Zhang

  • Chongqing Medical University, Chongqing, China

Senior Associate Editors

• Ronald A. Conlon, PhD

  • Case Western Reserve University School of Medicine, Cleveland, United States of America

• Fei Li, MD, PhD

  • University of Illinois at Chicago, Chicago, China

• Zhenkun Lou, PhD

  • Mayo Clinic Rochester, Rochester, United States of America

• Gloria H. Su, PhD

  • Columbia University Irving Medical Center, New York, United States of America

• Ni Tang, MD, PhD

  • Chongqing Medical University, Chongqing, China

• Lin Zhang, PhD

  • UPMC Hillman Cancer Center Shadyside, Pittsburgh, United States of America

• Peter B. Zhou, MD, PhD

  • Markey Cancer Center, Lexington, United States of America

Associate Editors

• Andreas Bikfalvi, MD, PhD

  • Angiogenesis and Cancer Microenvironment Laboratory, Talence, France

• Youquan Bu, PhD

  • Chongqing Medical University, Chongqing, China

• Tao-sheng Chen

  • St Jude Children's Research Hospital Department of Chemical Biology and Therapeutics, Memphis, United States of America

• Gerald W Dorn II, MD

  • Washington University in St Louis School of Medicine, Saint Louis, United States of America

• Hicham Drissi, Ph.D.

  • Emory University School of Medicine, Atlanta, United States of America

• Nancy Du, PhD

  • Weill Cornell Medicine, New York, United States of America

• Nickolai Dulin, PhD

  • University of Chicago Department of Medicine, Chicago, United States of America

• Richard Finnell, PhD, DABMGG

  • Baylor College of Medicine, Houston, United States of America

• Haian Fu, PhD

  • Emory University, Atlanta, United States of America

• Jim Hu, PhD

  • The Hospital for Sick Children, Toronto, Canada

• Aishun Jin, PhD

  • Chongqing Medical University, Chongqing, China

• Xi Li, PhD

  • Chongqing Medical University, Chongqing, China

• Yong Li, PhD

  • Cleveland Clinic Lerner Research Institute, Cleveland, United States of America

• Yong Liao, PhD

  • Chongqing Medical University, Chongqing, China

• Jun Liu

  • Mayo Clinic Hospital, Phoenix, United States of America

• Hua Lu, MD, PhD

  • Tulane University School of Medicine, New Orleans, United States of America

• Adam Marcus, PhD

  • Emory University, Atlanta, United States of America

• Sergey Orlov, MD, PhD

  • Department of Medical Sciences of the Russian Academy of Sciences, Moskva, Russian Federation

• Xiongzhong Ruan, MD, PhD

  • University College London Department of Renal Medicine, London, United Kingdom

• Jun Sun, PhD, AGAF

  • University of Illinois at Chicago, Chicago, United States of America

• Man-Sun Sy

  • Case Western Reserve University, Cleveland, United States of America

• Gopal Thinakaran, PhD

  • University of South Florida, Tampa, United States of America

• Ronald JA Wanders, PhD

  • University of Amsterdam, Amsterdam, Netherlands

• Da-Zhi Wang, PhD

  • Boston Children's Hospital and Harvard Medical School, Boston, United States of America

• Andre van Wijnen, PhD

  • Mayo Clinic Department of Biochemistry and Molecular Biology, Rochester, United States of America

• Geng-Sheng Wu, MD, PhD

  • Wayne State University, Detroit, United States of America

• Yaguang Xi, MD, PhD

  • LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER, New Orleans, United States of America

• Tingxiu Xiang, MD, PhD

  • Chongqing Medical University, Chongqing, China

• Jingwu Xie, PhD

  • Indiana University School of Medicine, Indianapolis, United States of America

• Qingbo Xu, MD, PhD

  • King's College London James Black Centre, London, United Kingdom

• Jian Yu, PhD

  • UPMC Hillman Cancer Center Shadyside, Pittsburgh, United States of America

• Xingxing Zang, PhD

  • Yeshiva University Albert Einstein College of Medicine, Bronx, United States of America

• Wei Zhou, PhD

  • Emory University, Atlanta, United States of America

Editorial Board Members

• Giuseppe Altavilla, MD, DSc

  • University of Messina Department of Human Pathology in Adulthood and Childhood, Messina, Italy

• Sergey Anisimov, MD, DSc

  • Almazov National Medical Research Centre, Sankt Peterburg, Russian Federation

• Jesus Avila, PhD

  • Autonomous University of Madrid Severo Ochoa Molecular Biology Centre, Madrid, Spain

• Anita Bellail, PhD

  • Indiana University School of Medicine, Indianapolis, United States of America

• Marcelo Bonini, PhD

  • Medical College of Wisconsin, Milwaukee, United States of America

• Vittorio Calabrese, PhD

  • University of Catania Department of Biomedical and Biotechnological Sciences, Catania, Italy

• Timothy Chan, MD, PhD

  • Memorial Sloan Kettering Cancer Center, New York, United States of America

• Guojun Chen, PhD

  • Chongqing Medical University, Chongqing, China

• Jianjun Chen, PhD

  • City of Hope Comprehensive Cancer Center Duarte, Duarte, United States of America

• Shiyuan Cheng, PhD

  • Northwestern University - Chicago, Illinois, United States of America

• Fabrizio Chiti, PhD

  • University of Florence, Firenze, Italy

• Hueng-Sik Choi, PhD

  • Chonnam National University Hormone Research Center, Gwangju, South Korea

• Junho Chung, MD, PhD

  • Seoul National University College of Medicine, Seoul, South Korea

• Cristian Coarfa, PhD

  • Baylor College of Medicine, Houston, United States of America

• Mushui Dai, PhD

  • Oregon Health & Science University, Portland, United States of America

• Aiko P.J De Vries, MD

  • Leiden University Medical Center Department of Nephrology, Leiden, Netherlands

• Danny N. Dhanasekaran, PhD

  • Oklahoma City University, Oklahoma City, United States of America

• Zhifang Dong, PhD

  • Chongqing Medical University, Chongqing, China

• Mingqing Du, PhD

  • University of Cambridge, Cambridge, United Kingdom

• Y. Murat ELÇİN, PhD

  • Ankara University and Turkish Academy of Sciences, Ankara, Turkey

• Matthias Eckhardt, PhD

  • University of Bonn, Bonn, Germany

• Guo-Chang Fan, PhD, FAHA

  • University of Cincinnati, Cincinnati, United States of America

• Rong Fan, PhD

  • Yale University, New Haven, United States of America

• Zhaohui Feng, PhD

  • Rutgers University New Brunswick, United States of America

• Jiliang Gao, PhD

  • National Institute of Allergy and Infectious Diseases, Bethesda, United States of America

• Leonard Girnita, MD, PhD

  • Karolinska Institute Cancer Research KI, Stockholm, Sweden

• Nicholas D.E. Greene, PhD

  • University College London, London, United Kingdom

• Deliang Guo, PhD

  • OHIO STATE UNIVERSITY, Columbus, United States of America

• Vsevolod V Gurevich, PhD

  • Vanderbilt University, Nashville, United States of America

• Chunhai Charlie Hao, MD, PhD, FRCPC

  • IU SIMON CANCER CENTER, Indianapolis, United States of America

• Vasif Hasirci, PhD

  • Acibadem University, İstanbul, Turkey

• Ming-Liang He, PhD

  • City University of Hong Kong, Kowloon, Hong Kong

• Xin He, PhD

  • University of Chicago, Chicago, United States of America

• Yu-Ying He, PhD

  • The University of Chicago Medicine, Chicago, United States of America

• Wenwei Hu, MD

  • Rutgers University New Brunswick, , United States of America

• George Huang, DDS, DSc

  • The University of Tennessee Health Science Center Center for Cancer Research, Memphis, TN, United States of America

• Esmaiel Jabbari, PhD

  • University of South Carolina, Columbia,, United States of America

• Hyeong-Reh Choi Kim, PhD

  • Wayne State University School of Medicine, Detroit, United States of America

• Lucia Languino

  • Thomas Jefferson University, Philadelphia, United States of America

• Irena Levitan, PhD

  • University of Illinois at Chicago College of Medicine, Chicago, United States of America

• Min Li, PhD

  • The University of Oklahoma Health Sciences Center, Oklahoma City, United States of America

• Wan-Ju Li, PhD

  • University of Wisconsin Madison, Madison, United States of America

• Wei Li, PhD

  • The University of Tennessee Health Science Center, Memphis, United States of America

• Jie Liang, PhD

  • University of Illinois at Chicago Department of Bioengineering, Chicago, United States of America

• Chuanju Liu, PhD

  • NEW YORK UNIVERSITY SCHOOL OF MEDICINE, New York, United States of America

• Pentao Liu, PhD

  • University of Hong Kong, Hong Kong, China

• Xiaoqi Liu, PhD

  • Purdue University Center for Cancer Research,

• Jun Lu, PhD

  • Yale University Department of Genetics, New Haven, United States of America

• Avudai Maran, PhD

  • Mayo Clinic College of Medicine Department of Orthopedic Surgery, Rochester, United States of America

• Valentina Massa, PhD

  • University of Milan, Milan, Italy

• Kimford Jay Meador, MD, FAAN, FRCPE

  • Stanford University School of Medicine, Stanford, United States of America

• Le Min, MD, PhD

  • Brigham and Women's Hospital, Boston, United States of America

• Eiji Miyoshi, MD, PhD

  • Osaka University, Osaka, Japan

• John F Moorhead, MD

  • University College London Department of Renal Medicine, London, United Kingdom

• Hammad Naveed, PhD

  • National University of Computer and Emerging Sciences, Islamabad, Pakistan

• Dietbert Neumann, PhD

  • Maastricht University, Maastricht, Netherlands

• Heyu Ni

  • St Michael's Hospital, Toronto, Canada

• Ming Pei, MD, PhD

  • West Virginia University Health Sciences Center, Morgantown, United States of America

• Russell Kirk Pirlo, PhD

  • US Naval Research Laboratory, Washington, United States of America

• Karen E. Pollok, PhD

  • Indiana University School of Medicine, Indianapolis, United States of America

• Zhijian Qian, PhD

  • University of Florida College of Medicine, Gainesville, United States of America

• Nader Rahimi, PhD

  • Boston University, Boston, United States of America

• Brian B. Rudkin, PhD

  • Stem Cell and Brain Research Institute, Bron, France

• Roger Schneiter, PhD

  • University of Fribourg, Fribourg, Switzerland

• Hiroshi Shibuya, PhD

  • Tokyo Medical and Dental University, Tokyo, Japan

• Jinglin Song, DDS, PhD

  • Chongqing Medical University, Chongqing, China

• Massimo Stefani, PhD

  • University of Florence, Firenze, Italy

• Zhongjie Sun, MD, PhD

  • University of Tennessee Health Science Center College of Medicine Memphis, Memphis, United States of America

• Young-Joon Surh, PhD

  • Seoul National University College of Pharmacy, Seoul, South Korea

• Xiaodi Tan, MD

  • Northwestern University - Chicago, Illinois, United States of America

• Qian Tao, PhD

  • The Chinese University of Hong Kong, Shatin, Hong Kong

• Wei Seong Toh, PhD

  • National University of Singapore, Singapore, Singapore

• Ratna K. Vadlamudi, PhD

  • University of Texas Health Science Center at San Antonio, San Antonio, United States of America

• Donald Vander Griend, PhD

  • University of Illinois at Chicago, Chicago, United States of America

• Zac Varghese, PhD

  • University College London Department of Renal Medicine, London, United Kingdom

• Alexander Vorotnikov, PhD

  • Nacional'nyj issledovatel'skij tehnologiceskij universitet MISiS Gornyj institut, Moskva, Russian Federation

• Gang Wang, MD, PhD

  • Shanghai Jiao Tong University School of Medicine, Shanghai, China

• Jing Wang, PhD

  • UNIVERSITY OF NEBRASKA MEDICAL CENTER, Omaha, United States of America

• Qien Wang, PhD

  • OHIO STATE UNIVERSITY, Columbus, United States of America

• Tian-Li Wang, PhD

  • Johns Hopkins University, Baltimore, United States of America

• Qiou Wei, MD, PhD

  • Markey Cancer Center, Lexington, United States of America

• Erxi Wu, PhD

  • Texas A&M University Kingsville, Kingsville, United States of America

• Lizi Wu, PhD

  • University of Florida, Gainesville, United States of America

• Wen-Shu Wu, PhD

  • University of Illinois at Chicago, Chicago, United States of America

• Zhaohui Wu, MD, PhD

  • The University of Tennessee Health Science Center, Memphis, United States of America

• Shuli Xia, PhD

  • Johns Hopkins University, Baltimore, United States of America

• Yin Xiao, PhD

  • Queensland University of Technology Institute of Health and Biomedical Innovation, Brisbane, Australia

• Zhongjian Xie, MD, PhD

  • University of California San Francisco, San Francisco, United States of America

• Wei Xu, PhD

  • University of Wisconsin Madison, Madison, United States of America

• Ying Xu, PhD

  • The University of Georgia, Athens, United States of America

• Chunhong Yan, PhD

  • Augusta University Medical College of Georgia, Augusta, United States of America

• Jun Yan, MD, PhD

  • University of Louisville School of Medicine, Louisville, United States of America

• Peter Yun-zhi Yang, PhD

  • Stanford University Yang Laboratory, Stanford, United States of America

• Xiaolu Yang, PhD

  • University of Pennsylvania, Philadelphia, United States of America

• Kiyotsugu Yoshida, MD, PhD

  • Jikei University School of Medicine, Minato-Ku, Japan

• Jiwang Zhang, MD

  • Loyola University Medical Center, Maywood, United States of America

• Rugang Zhang, PhD

  • Wistar Institute, Philadelphia, United States of America

• Ruiwen Zhang, MD, PhD

  • University of Houston College of Pharmacy, Houston, United States of America

• Yuanyuan Zhang, MD, PhD

  • Wake Forest University, Winston-Salem, United States of America

• Zhiqian Zhang, MD, PhD

  • Peking University Health Science Centre, Beijing, China

• Wenge Zhu, PhD

  • The George Washington University, Washington, United States of America

• Hui Zong, PhD

  • University of Virginia, Charlottesville, United States of America

• Wei-xing Zong, PhD

  • Rutgers The State University of New Jersey, New Brunswick, United States of America

Statistics Editors

• Dezheng Hou, MD, PhD

  • University of Chicago, Chicago, United States of America

• Xiaoyan Iris Leng, MD, PhD

  • Wake Forest University, Winston-Salem, United States of America

• Yinglin Xia, PhD

  • University of Illinois at Chicago, Chicago, United States of America

Senior Advisory Board

• Xuetao Cao, MD, PhD

  • Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

• Jing Cheng, PhD

  • Tsinghua University academician of Chinese Academy of Engineering, Beijing, China

• Wafik S El-Deiry, MD, PhD, FACP

  • Fox Chase Cancer Center, Philadelphia, United States of America

• Charis Eng, MD, PhD, FACP

  • Cleveland Clinic, Cleveland, United States of America

• Daiming Fan, PhD

  • Xijing Hospital, Xian, China

• Eric Fearon, PhD

  • University of Michigan, Ann Arbor, United States of America

• Wei Gu, PhD

  • Columbia University Institute for Cancer Genetics, New York, United States of America

• Chuan He

  • University of Chicago, Chicago, United States of America

• Kenneth W. Kinzler, PhD

  • Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

• Lanjuan Li, MD

  • First Hospital of Zhejiang Province, Hangzhou, China

• Guido Marcucci, MD

  • Beckman Research Institute, Duarte, United States of America

• Sanford Markowitz, MD, PhD

  • Case Western Reserve University School of Medicine, Cleveland, United States of America

• Markus Müschen, MD, PhD

  • City of Hope Comprehensive Cancer Center Duarte, Duarte, United States of America

• Anil Rustgi

  • Herbert Irving Comprehensive Cancer Center, New York, United States of America

• Xiao-Fan Wang

  • Duke University, Durham, United States of America

• Zheng-guo Wang, MD

  • Army Medical University, Chongqing, China

• Anthony Wynshaw-Boris, MD, PhD

  • Case Western Reserve University and Cleveland Medical Center, Cleveland, OH, USA, Cleveland Ohio, United States of America

• Huangming Yang, PhD

  • Third Military Medical University academician of Chinese Academy of Engineering, Chongqing, China

• Susheng Zheng, MD

  • Zhejiang University, Hangzhou, China

• Nan-Shan Zhong, MD

  • Guangzhou Institute of Respiratory Disease, Guangzhou, China

• Honghao Zhou, MD

  • Central South University, Hunan, China

Link to the Special Issue:

Focus on the Primary Immunodeficiency Diseases. 

Genes & Diseases. Volume 7, Issue 1. March 2020.

Cover Story

Primary immunodeficiency diseases (PIDDs) are a group of the most clinically challenging diseases in children. They are heterogeneous disorders caused by inborn errors in one or more components of the immune system. With the increased awareness and applications of next generation sequencing technology in recent years, over 350 distinct disorders have been discovered. However, a large number of PIDDs are believed to be unidentified. Mechanistically, PIDDs may affect both innate immunity and/or adaptive immunity. In this special issue, the guest editors Dr. Surjit Singh, Dr. Adrian Thrasher and Dr. Xiaodong Zhao invited a panel of physician investigators to discuss the pathogenesis and clinical management of PIDDS.  Due to the impaired host defense and aberrant immunity, PIDDs clinically manifest as infections, as well as features of immune dysregulation such as autoimmunity, lymphoproliferation, autoinflammation and malignancy. In many cases, PIDDs are treatable and curable. Immunoglobulin G replacement is the cornerstone of therapy for antibody deficiency. Hematopoietic stem cell transplantation provides a cure for many forms of PIDDs. Gene therapy has also shown promising results in a couple of disorders. More efforts should be devoted to the improvement of their clinical management and newborn screening. An artistic rendition in the cover image reveals that the immune system (the umbrella and belts) of a baby may be attacked by pathogens (rains) and cause alterations at DNA level, leading to the production of defective immune cells.

Link to the Special Issue:

Hepatocellular Carcinoma - from bench to bedside.

Genes & Diseases. Volume 7, Issue 3. September 2020.

Cover Story

Professor Zhao-You Tang—celebrating his 65-year academic career in hepatic surgical oncology in China.  Professor Tang received his M.D. from Shanghai Medical College (currently Fudan University Shanghai Medical College, Shanghai, China) in 1954, and started his academic career in the Department of Surgery, Zhongshan Hospital of Fudan University Shanghai Medical College, where he has been practicing and teaching surgical oncology for 65 years. Professor Tang is an internationally renowned liver cancer investigator and a pioneer of surgical treatment of small and sub-clinical liver cancer. His scholarly accomplishments have won him international recognitions and respect by his peers in the field of liver cancer research and its surgical treatment. Professor Tang has held numerous academic and leadership roles over the years, including the President of Shanghai Medical University (1988-1994), the Vice President of the Chinese Medical Association, and a Council Member of the Union for International Cancer Control (UICC) (1990-1998). He also established the Liver Cancer Institute at Zhongshan Hospital of Fudan University and served as the inaugural director of the Institute. Professor Tang has published numerous original papers on liver cancer and edited several highly popular textbooks in Chinese and English, such as Primary Liver Cancer (1981 and the English Edition in 1989), Contemporary Oncology (1993), and Subclinical Liver Cancer (1985).  His distinguished achievement and outstanding contributions have won him numerous distinctions, including an election to the Chinese Academy of Engineering (CAE) (1994), and the selection as an honorary fellow of the American Surgical Association (2005) and Japan Surgical Society (2007), respectively. To celebrate Professor Tang’s 65-year career in academic medicine, we compiled this special issue on liver cancer, which were contributed by several of his trainees, and guest edited by Dr. Yong Liao of Chongqing Medical University, Chongqing, China. The cartoonish cover image illustrates Professor Tang’s role in medical education and patient care, as well as in inspiring new generations of liver cancer researchers and clinicians.

Link to the Special Issue:

COVID-19 Pandemic: We Don't Know What We Don't Know.

Genes & Diseases. Volume 7, Issue 4. December 2020.

Cover Story

Coronavirus is the common name for Coronaviridae, which consists of  a large group of animal viruses and is organized in two sub-families, 5 genera, 26 sub-genera, and 46 species. Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses and can infect amphibians, birds, and mammals. Human coronaviruses were first identified in the mid-1960s. Most people commonly get infected with human coronaviruses 229E, NL63, OC43, and HKU1, while sometimes coronaviruses that infect animals can evolve and infect humans and become a new human coronavirus, such as SARS-CoV and MERS-CoV. With very little warning, a major outbreak of the COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2 infection. In this issue, several articles documented the clinical and immunological characteristics, and potential therapeutics or vaccines of COVID-19. Nonetheless, our understanding about the exact pathogenic mechanism of COVID-19 is limited so SARS-CoV-2 coronavirus remains as elusive as a ghost. We can only hope the anti-COVID-19 researchers worldwide act as the Chinese mythological figure, ZHONG KUI, whose virtuoso is to catch and destroy ghosts, as depicted in the cover.

Link to the cover story: 

Pakvasa M., et al. Notch signaling: Its essential roles in bone and craniofacial development. Genes & Diseases. 2021, 8(1):8-24.

Cover Story

The Notch signaling pathway is a complex cell-cell communication network that regulates a host of essential cellular processes including embryonic development and skeletal homeostasis. Mutations in the Notch signaling pathway during skeletal development lead developmental deformities such as brachydactyly, spondylocostal dysostosis, and even soft tissue tumors. In this issue, Pakvasa M et al surveyed the important roles of Notch signaling in bone and skeletal development, with a focus on the contributions of Notch signaling to craniofacial embryogenesis and craniofacial development in the context of diseases and therapies. To certain extents, the Notch signaling pathway in the skeletal system acts like the lotus root fiber networks that are extensively interconnected and regulate the growth and rebirth of lotus roots, like the famed “Nezha” character in Chinese fairytale, in which a broken lotus root with fibers resembles the Notch signaling network at a bone fracture site to repair the broken trabecular system. (The cover story was written by Dr. Huijie Zhang. The Illustration was drawn by Yonglong Lu, Huiyou Wu and Qiushi Wang.)

Link to the cover story: 

Singh M.P., et al. Molecular subtypes of colorectal cancer: An emerging therapeutic opportunity for personalized medicine. Genes & Diseases. 2021, 8(2):133-145.

Cover Story

Colorectal cancer (CRC) is one of the most common types of cancer and poses a formidable challenge to global public health. CRC incidence rates are approximately 3-fold higher in the developed countries than that in the developing countries. Fortunately, CRC represents one of the best understood human malignancies as the molecular genetic events such as mutations and epigenetic modifications contributing to the multi-step tumorigenesis process have been reasonably well elucidated. Nonetheless, genomewide large-scale analyses indicate CRC is highly heterogeneous with different pathological and genetic signatures. It is critical to identify and characterize sets of biomarkers for various molecular subtypes in order to select effective therapy regimen since “one drug fits all’ model may not work for the patients who even display similar pathological changes. In this issue, Singh MT et al overviewed the molecular subtypes of CRC based on its underlying molecular and genomic alterations. Using prognostic biomarkers along with pathological staging, molecular subtypes-based therapies should offer a new framework for targeted and personalized therapies in clinical settings. As implied in one of the famous Chinese legends of the Three Kingdoms, the Shuo Kingdom Prime Minister Liu Bei was saved by a precision shooting of a Chinese polearm (or halberd) from the Han Dynasty Warrior Lv Bu as illustrated in the cover image. It is conceivable that CRC patients receiving immune checkpoint blockade therapy and other chemotherapies with a special emphasis on CRC molecular subtypes should attain better clinical outcomes, and thus are greatly benefited from precision oncology. (Illustration credits: Huijie Zhang, PhD and Qiushi Wang. )

Link to the cover story: 

Sun T., et al. Regulation of ferroptosis in cancer cells by YAP/TAZ and Hippo pathways: The therapeutic implications. Genes & Diseases. 2021, 8(3):241-249.

Cover Story

Ferroptosis is a novel form of iron-dependent programmed cell death (PCD) characterized by mitochondria shrinkage, membrane content condensation, and the accumulation of lipid peroxidation. While the importance and disease relevance of ferroptosis is gaining recognition, much remains unknown about various genetic and non-genetic determinants of ferroptosis.  In this issue, Drs. Tianai Sun and Jen-Tsan Chi provided an overview about the roles of YAP and Hippo pathways in regulating ferroptosis in cancer cells. The evolutionarily-conserved Hippo pathway exerts potent tumor suppression effect.  Its dysregulation contributes to apoptosis evasion, tumorigenesis, cancer metastasis, and the development of treatment resistance, through an aberrant activation of the downstream co-activators YAP/TAZ. Ferroptosis and apoptosis are regulated by the cellular contact and density through the Hippo and YAP/TAZ pathways. YAP/TAZ activation under low cell density confers apoptosis resistance and renders cancer cells sensitivity to ferroptosis. On the contrary, under high cell density with extensive cell-cell contacts, activated Hippo signaling degrades YAP/TAZ and retains them cytosolically, leading to apoptosis activation but ferroptosis inhibition.  Thus, the balanced regulation of Hippo and YAP/TAZ activities may determine the cell fate committed to ferroptosis vs. apoptosis.   It is conceivable that ferroptosis induction may have therapeutic potential to treat YAP/TAZ-activated chemoresistant and metastatic cancers. The cover image illustrates how delicately the front (e.g., upstream HIPPO) and rear (e.g., downstream YAP) Buddhist monks coordinate on uneven ground may determine how much water (e.g., ion supply pool) will be left in the barrel (e.g., cancer cells), leading to ferroptosis vs. apoptosis.  (Illustration credits: Huijie Zhang, PhD and Zijian Qu. )

Link to the cover story: 

https://www.sciencedirect.com/journal/genes-and-diseases/vol/8/issue/4

Cover Story

The Novel Coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged and caused the pandemic Coronavirus Disease 2019 (COVID-19) since 2019. While respiratory symptoms are the early and typical signs after infection of SARS-CoV-2, it has been subsequently documented that a subset of COVID-19 patients experience mild to serious gastrointestinal symptoms, such as diarrhea, vomiting, nausea, and abdominal pain. Emerging clinical and experimental evidence indicates that gastrointestinal tract and many other tissues, such as liver, heart, blood vessels, kidneys, and brain, can be targeted by SARS-CoV-2. In this issue, Zhang et al. systemically summarized the relationships among COVID-19 disease, gastrointestinal symptoms and intestinal microbiota. The detection of viral RNA and live virus in the stool samples of COVID-19 patients raises the possibility of oral-fecal transmission of COVID-19. Thus, understanding the pathogenesis of SARS-CoV-2 virus, and the associations among COVID-19, inflammation, intestinal microbiota, and lung microbiota may aid us to develop novel diagnosis technology and clinical treatments/therapies, leading to an integrated and systematic prevention and control of COVID-19 globally. The cartoonish cover image illustrates the invasion of SARS-CoV-2 starts in oral cavity (upper cliff), through potential oral-fecal transmission, down to gastrointestinal tract (water flow) where the gut microbial flora may be disturbed. Ultimately, the virus may venture out to liver or other organs (rocks).  (Illustration credits: Huijie Zhang, PhD and Zijian Qu.)

Link to the cover story: 

https://www.sciencedirect.com/journal/genes-and-diseases/vol/8/issue/5

Cover Story

Emerging evidences strongly suggest that microbiota including bacteria, viruses and archaea, may greatly impact many physiological processes and hence our health. Gut microbiota play major roles in metabolic functions of fermenting and absorbing undigested carbohydrates, energy harvesting and storage. Thus, dysbiosis of gut microbiota can not only cause intestinal dysfunctions, which may lead to inflammatory, immune, and infectious diseases, but also influence the physiological functions of extra-intestinal organs or tissues via microbial translocation or metabolisms. In this issue, Zhang et al. reviewed formation and biological role of the breast microbiome, which may be sourced from the gut microbiota through the skin-breast route or due to the increased intestinal permeability. Both of the breast and intestinal microbiota contribute to maintain breast health. The review also highlighted novel roles of bacterial products in the development and progression of breast cancer. For example, bacterial metabolite queuine (Q) can modify the wobble anticodon position of specific tRNAs in human cells, and regulate genes critical in tight junctions and migration in human breast cancer. The cover illustration depicts the translocation pathway of the gut microbiota (the old man and winding stalk) to the breast (flower), whereas the waving PU SHAN, a palm-leaf fan, imitates the bacterial metabolite queuine (Q) to exacerbate the effect of gut-breast microbiome on breast cancer progression. The Chinese characters “JUN JIE” means the Kingdom of microbiota. (Illustration credits: Huijie Zhang, PhD and Zijian Qu).

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Cover Story

The establishment of 3D culture system for gut organoids (also known as “mini gut”) has not only ushered a new era for intestinal stem cell research, but also led to the creations of organoids from a wide range of tissues and organs of human and animal origins. Nonetheless, the cultured “mini gut” organoids consist of heterogeneous cell populations, and are rather costly to maintain. Furthermore, it is technically challenging to introduce genetic changes into specific types of cells in 3-D organoids. In this issue, Wu et al established a conditionally-immortalized mouse intestinal crypt cell line, designated as ciMIC. They showed the ciMIC cells exhibited long-term proliferative capability while retaining biological characteristics of intestinal epithelial stem cells. The introduction of mutant KRAS rendered the ciMIC cells malignant transformation phenotype, suggesting that the ciMIC cells may be used as valuable intestinal epithelial progenitors for extensive genetic manipulations to uncover the molecular pathogenesis of intestinal tumors. As illustrated in the cover image, the iMIC organoids (on the left hand of Monkey King, a mighty ancient Chinese supernatural being), unlike the the wild type organoids (on the right hand), can serve as recipients of numerous genetic manipulations (including activating oncogenes or mutant tumor suppressor genes) for intestinal tumor studies. (Illustration credit: Ning Wang, MD, PhD, Huijie Zhang, PhD, and Zijian Qu).

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Cover Story

CCR5 and its ligand CCL5 play a crucial role in inflammation, and induce the adhesion and migration of different T cell subsets during immune responses. Recent studies have implicated CCL5 and CCR5 in various pathological processes including inflammation, chronic diseases, and cancers, as well as the infection ofSARS-CoV-2. Thus, CCL5/CCR5-targeted therapeutics has been extensively developed. Classic small molecule inhibitors, such as Maraviroc, Cenicriviroc and MET-CCL5, have shown promising outcomes in clinical trials. In this issue, Zeng et al. conducted a thorough review by focusing on the molecular regulators and upstream or downstream signaling events of the CCL5/CCR5 axis, and its pathogenic roles in human diseases. Their review further highlighted several classic targeted therapies and clinical trials in CCR5-related diseases.  It is expected that advances in many fields including immunology, pathology, and gene editing, would lead to the development of more therapeutic strategies specifically targeting CCL5/CCR5. The cover illustration depicts the structure of CCL5/CCR5 complex reflected in the water as the coiled ribbons waved by the dancer (Illustration credit: Xia-Wei Wei, PhD, Huijie Zhang, PhD, and Qiushi Wang).

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Cover Story

Noncoding RNAs (ncRNAs) account for the vast majority of  the human transcriptome and have been implicated in cancer diagnosis and prognosis.  Many ncRNAs, such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs), small nucleolar RNAs (snoRNAs), play important roles in regulating cellular processes, and contribute to pathogenic conditions including cancer development. Thus, it is conceivable that ncRNAs can be used potential bio-markers in the early diagnosis and prognosis of cancer. More recently, increasing attention has been paid to the transfer RNA (t-RNA)-derived small RNAs (tsRNAs), a class of small noncoding RNA generated from precursor or mature tRNAs which have been shown to participate in diverse physiological and pathological processes. In this issue, Zuo et al. developed a novel tsRNA-based diagnostic and prognostic signature for liver cancer. The reported tsRNA-based random forests diagnostic model can segregate low-risk and high-risk patients and effectively predict 5-year disease-free survival. The cover illustration depicts the potential conversion of tRNAs to tsRNAs, in which the tsRNA (represented by the tail of the rightmost mouse) can be generated from tRNA (the leftmost mouse) and function as efficient molecular markers (represented by the black thread) for the early diagnosis and prognosis liver cancer (represented by the candlelight flames) (Illustration credit: Huijie Zhang, PhD, and Zijian Qu).

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Cover Story

Kidney diseases represent a major global public health problem and impose significant financial burdens on the affected individuals. As one of the major organs in human body, kidney regulates the whole-body homeostasis through approximately one million nephrons. Any structural damages can substantially impact the kidney functions that regulate acid-base balance, electrolyte concentrations, extracellular fluid volume, and blood pressure, as well as being implicated in inflammation and diabetes. Furthermore, kidney is not only a major target organ of toxic side effects, but also highly vulnerable to drug-induced renal impairment.  Inspired from the successful generation of organoids from either pluripotent stem cells (iPSCs) or adult stem cells (ASCs) by strictly regulating key signaling pathways, human kidney organoids with differentiation potential have been established in three-dimensional systems. In this issue, Wu M. et al. summarized the investigations and potential clinical applications of human kidney organoids in studying kidney development, diseases modeling, drug nephrotoxic testing, biobanking, precision medicine and regenerative therapy of renal diseases.  As inspired by one of the famous Chinese legends of Fuxi’s diagram of the eight trigrams, the kidney organoids (represented by the turtle shell) derived from kidney (depicted as the white flying dragon around the turtle) can be used to investigate many basic, translational and clinical aspects of renal diseases  by researchers worldwide (represented by the well-respected wise man Fuxi) (Illustration credit: Huijie Zhang, PhD, and Zijian Qu).

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Cover Story

Periodontal ligament (PDL) connects alveolar bone (AB) and cementum to form the periodontium. This complex structure plays a vital role in orthodontic tooth movement and homeostatic maintenance of tooth supporting apparatus, as well as inperiodontal diseases (PD). PD involving inflammatory response, such as periodontitis, affects both soft and mineralized periodontal tissues, as a common cause of tooth loss worldwide. PDL not only acts as a barrier for protecting from pathogens and provides sensory input for the mastication system, but also serve as a renovator for the destructed periodontal tissue by mobilizing numerous types of cells including stem cells and fibroblasts. However, the interactions between PDL and PD pathogenesis in vitro platforms and pre-clinical models have not been fully understood. In this issue, Vurat et al developed a three-dimensional bioprinted multi-cellular microtissue model to mimic the periodontal ligament-alveolar bone biointerface. These novel constructs showed a great mechanical properties and biocompatibility for osteoblast and fibroblast migration and location in PDL layer. Thus, the assembly of multi-cellular periodontal/osteoblastic microenvironment onto the developed PDL-AB biointerface may serve as a valuable preclinical platform to assess the interactions between PDL and mineralized tissues. As inspired by Chinese mural “FEI TIAN”, the fairy flies through the cementum and alveolar bone complex modeled by the PDL-AB microtissue. The inner connections between alveolar bone and cementum are integrated by the periodontal ligament-mimicking silk ribbons from her wrists. (Illustration credit: Huijie Zhang, PhD, and Qiushi Wang).

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Cover Story

Somatic activating mutations in the epidermal growth factor receptor (EGFR) are one of the most common oncogenic drivers in human cancers. While molecular agents targeting EGFR signaling pathways have shown robust clinical efficacy, patients inevitably develop acquired resistance. Interaction between the B7 family and their receptor CD28 family provides critical costimulatory and coinhibitory signals that regulate immune cell-mediated anti-tumor immunity, which can thereby be exploited by tumors as immune evasion pathways. Recent studies have demonstrated that B7/CD28 family members, including new members B7x and HHLA2, in cancers harboring activating EGFR mutations were upregulated. B7x and HHLA2 were discovered by Dr. Xingxing Zang in 2003 and 2013 respectively as immune checkpoints of great importance to human cancers. Given their roles in suppressing anti-tumor immunity, the upregulated expression of B7x and/or HHLA2 triggered by EGFR mutants may contribute to resistance to EGFR-targeted therapies by creating an immunosuppressive tumor microenvironment. Therefore, targeting EGFR signaling in combination with cancer immunotherapies, particularly immune checkpoint inhibitors targeting new B7/CD28 members B7x or HHLA2, can lead to more effective cancer in the clinic. As inspired by Chinese traditional Lion Dance, the waving little lion (i.e., mutant EGFR) stirs the wind, and then the wind feeds the fire (i.e., cancer drug resistance), which leads to a bigger lion (i.e., B7x & HHLA2) show, illustrating the complicated inner connections between HHLA2 & B7x and EGFR signaling. (Illustration credit: Xingxing Zang, PhD, Huijie Zhang, PhD, and Zijian Qu).

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Cover Story

Transfer RNAs (tRNAs) are essential for protein synthesis, while mature or pre-tRNAs can be cleaved into tRNA-derived small RNAs (tsRNAs). Currently, tsRNAs are divided into two classes, the tRNA-derived stress-induced RNA (tiRNAs) and the tRNA-derived fragments (tRFs), both of which play important roles in cell proliferation, migration, cell cycle, and apoptosis, in addition to their regulatory roles in gene silencing, RNA stability, reverse transcription and translation. The abnormal expression of tsRNAs is associated with the development of various human diseases including cancers. Recent advances in high-throughput sequencing technology and bioinformatics have further facilitated the investigation of the different structures and potential functions of tsRNAs. In this issue Wang Y et al provided a comprehensive review on the classification, biogenesis, and mechanism of action of tsRNAs, as well as their roles in cancers. Ultimately, tsRNAs may serve as potential diagnostic biomarkers and/or valid treatment targets for cancers, neurodegenerative diseases, viral infectious diseases, and metabolic diseases. As inspired by Chinese historical legend “Jiangtaigong Fishing”, tsRNAs are depicted as fishing indicators (various fishes and seaweeds etc.), resembling biomarkers for diagnosis and valuable therapeutic targets of human diseases (Illustration credit: Huijie Zhang, PhD, and Zijian Qu).

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https://www.sciencedirect.com/journal/genes-and-diseases/vol/10/issue/1

Cover Story

CCR5 and its ligand CCL5 play a crucial role in infl ammation, and induce the adhesion and migration of diff erent T cell subsets during immune responses. Recent studies have implicated CCL5 and CCR5 in various pathological processes including infl ammation, chronic diseases, and cancers, as well as the infection of SARS-CoV-2. Thus, CCL5/ CCR5-targeted therapeutics has been extensively developed. Classic small molecule inhibitors, such as Maraviroc, Cenicriviroc and METCCL5, have shown promising outcomes in clinical trials. In this issue, Zeng et al. conducted a thorough review by focusing on the molecular regulators and upstream or downstream signaling events of the CCL5/CCR5 axis, and its pathogenic roles in human diseases. Their review further highlighted several classic targeted therapies and clinical trials in CCR5-related diseases. It is expected that advances in many fi elds including immunology, pathology, and gene editing, would lead to the development of more therapeutic strategies specifi cally targeting CCL5/ CCR5. The cover illustration depicts the structure of CCL5/CCR5 complex refl ected in the water as the coiled ribbons waved by the dancer (Illustration credit: Xia-Wei Wei, PhD, Huijie Zhang, PhD, and Qiushi Wang).

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https://www.sciencedirect.com/journal/genes-and-diseases/vol/10/issue/2

Cover Story

Posttranscriptional modifi cations of messenger RNA (mRNA) and noncoding RNA molecules play a critical role in regulating RNA stability and subsequent gene expression levels. N6-methyladenosine (m6A) RNA modifi cation represents one of the most common, abundant, and conserved posttranscriptional modifi cations in eukaryotes. The m 6A modifi cation can be dynamically installed by m6A methyltransferases (METTL 3/144 and cofactors), or removed by demethylases (such as FTO and ALKBH5). RNA m 6A modifi cation can regulate gene expression and accelerate the development of cancer. However, little is known about the exact role of m 6A modifi cation in regulating long non-coding RNA (lncRNA) and lncRNA-mediated tumorigenesis, particularly in pancreatic ductal adenocarcinoma (PDAC). In this issue, Peng et al reported that a previously uncharacterized lncRNA, LINC00901, promotes the growth and metastasis of pancreatic cancer cells. The expression of LINC00901 can be regulated by m 6A modifi cation, which positively regulates MYC through upregulating IGF2BP2, a known RNA binding protein that can enhance MYC mRNA stability, while YTHDF1 serves as a reader for the m 6A modifi ed LINC00901 at two conserved sites and downregulates LINC00901 level. As illustrated in the cover image, the LINC00901-IGF2BP2-MYC axis can drive PDAC (Crab) progression in the presence of m 6A modifi cation (Illustration credit: Huijie Zhang, PhD, and Zijian Qu).

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RNA interference (RNAi) is a conserved biological process for degrading target messenger RNA (mRNA). RNAi has been considered as a potential novel therapeutic strategy to treat human diseases including cancer. However, a major challenge is how the RNAi oligonucleotides can avoid nuclease degradation, rapid renal clearance, non-specific delivery, poor cellular uptake, inflammatory response, and then gain access to modulate target transcripts in the cytosol. Tanno et al. developed a novel targeted small RNA delivery platform that comprises of three oligonucleotides: a guide RNA sequence, part of a passenger sequence linked to a DNA aptamer via a PEG linker, and another passenger sequence conjugated to a hydrophobic cholesterol core. This cation-dependent nano-platform not only extends small RNA’s half-life and cancer cell-targeting specificity but also allows escape from the endosomal compartment for efficient target mRNA silencing. The cover image is inspired by the Chinese idioms from Shih Chi (a book of history), “Bai Bu Chuan Yang” means shooting an arrow (the therapeutic RNA nanoparticles) through a willow leaf (cancer cells) a hundred steps away with great precision (Illustration credit: Huijie Zhang, PhD, and Zijian Qu).

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With the completion of Human Genome Project (HGP), deep sequencing technologies gradually reveal a vast majority of human genomes to be transcribed into RNAs. Only a small portion of the transcripts (also known as mRNAs) can be translated into proteins, and most of the remaining RNAs are as non-coding RNAs (ncRNAs) including long non-coding RNAs (lncRNAs). Among LncRNAs, H19 is one of the fi rst identifi ed regulatory lncRNAs, and has recently gained increasing attentions due to its essential roles in regulating many physiological and/or pathological processes, such as embryogenesis, development, tumorigenesis, osteogenesis, and metabolism. Although not fully understood, H19 has been shown to regulate gene expression by serving as competing endogenous RNAs (CeRNAs), Igf2/H19 imprinted tandem gene, and modular scaff old, cooperating with H19 antisense, and acting directly with other mRNAs or lncRNAs. Currently, Liao J et al provided a systematic up-to-date review on currently known functions of H19, which should inspire more indepth studies to delineate the detailed molecular, cellular, epigenetic, and genomic regulatory mechanisms underlying the physiological and pathological roles of H19. As depicted in the folk lion dances in China, the H19 resembles the powerful and versatile lion, and its biological functions are carried out by wellcoordinated individual performers (Illustration credit: Ning Hu, PhD, Huijie Zhang, PhD, and Zijian Qu).

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Circular RNAs (circRNAs) are a novel class of noncoding RNAs that widely exist in eukaryotes. They exhibit a covalently closed-loop structure produced from precursor mRNA (pre-mRNA) through backsplicing mechanism. Increasing attentions have been drawn to their novel functions in recent years. It is known that circRNAs play important roles in numerous physiological and pathological processes, as well as in regulating the biological activities of stem cells such as self-renewal and diff erentiation, migration, apoptosis, and aging. Furthermore, circRNAs may serve as new targets in stem cell therapy due to their regulation in stem cells. However, the underlying relationships between circRNAs and stem cells are still being explored. In this issue, Wang et al reviewed the eff ects of circRNAs on stem cells and surveyed the biological roles of stem cell-derived exosomal circRNAs as depicted in the cover image. Overall, this review provides insightful perspectives about the eff ects of circRNAs on stem cell functions (Illustration credit: Huijie Zhang, PhD, and Zijian Qu).

 

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The human eye is a complex sensory organ consisting of multiple layers of highly specialized cells that react to visible light and allow humans to use visual information for seeing things, keeping balance, and maintaining circadian rhythm. Among the cellular layers, the retinal pigment epithelium (RPE) and the choroid play critical roles in maintaining vision. However, little is known about the changes that occur in the eye as human’s age. In this issue, Huang et al conducted the single-cell transcriptomic analysis and thoroughly examined the genes expressed by individual cells within the RPE and choroid. Such analysis yielded a wealth of new insights into the cellular composition and functions of these layers, and revealed previously unknown dynamic changes and interactions between cells. Furthermore, the authors identifi ed signifi cant alterations in gene expression profi les between young and old individuals, as well as diff erences between central and peripheral regions of the RPE and choroid as comically illustrated in the cover image, which may have signifi cant implications for the diagnosis and treatment of age-related retinal diseases, such as age-related macular degeneration (Illustrated by Lulin Huang, PhD, Huijie Zhang, PhD, and Zijian Qu).

 

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As the most abundant internal modifi cation in mRNA, N⁶-methyladenosine (m⁶A) plays critical roles in normal bioprocesses and tumorigenesis by regulating mRNA fates. Here, Zhang et al reported that YTHDF2, the first identified “reader” protein of m⁶A, facilitated miR-126 maturation to promote the development and progression of acute myeloid leukemia (AML), whereas both YTHDF2 and miR-126 were aberrantly overexpressed. Mechanistically, YTHDF2 recognized the m6A modifi cation on precursor miR-126 (pre-miR-126) and facilitated its processing to mature miR-126 by recruiting AGO2 to m⁶A-modifi ed pre-miR-126, leading to the increased maturation/expression of miR-126 and development of AML. The cover image depicts how YTHDF2 (the magician) regulates the maturation of miR-126 as an m⁶A reader, underlying the oncogenic role of YTHDF2 in AML. Overall, this study highlights the critical role of YTHDF2 and m⁶A modification in the maturation of precursor miRNAs, which contributes to tumorigenesis, as illustrated in the cover image (Illustration credit: Zheng Zhang, Zhenhua Chen, Jianjun Chen, Huijie Zhang and Zijian Qu).

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Emerging evidence demonstrates that transfer RNA (tRNA)-derived small RNAs (tsRNAs) act as a new type of noncoding small RNAs and play an important role in the pathogenesis of human diseases. Based on nuclease cleavage sites on tRNAs, tsRNAs can be divided into two categories: tRNA halves (tiRNAs) and tRNA-derived fragments (tRFs). Their biosynthesis is tissue-specific and regulated by tRNA modifications. The current modes of action for tsRNAs include transcriptional gene silencing, post-transcriptional gene silencing, nascent RNA silencing, translation regulation, rRNA regulation and reverse transcription regulation, which may underly the diverse biological functions of tsRNAs in tumors. Zhang et al reviewed the clinical implications of tsRNA in cancers and discussed their potential as novel biomarkers and/or therapeutic targets for cancers. As inspired in dandelion in the illustration, tsRNAs are derived from tRNAs and signifi cantly impact tumorigenesis with important implications in cancer diagnosis and therapy (Illustration credit: Yu Zhang, Huijie Zhang and Zijian Qu).

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The Wnt signaling pathway is a key component of tissue development and homeostasis in many species. Lipid-modified signaling molecules known as Wnt proteins activate both the canonical ( ß-catenin dependent) and non-canonical (ß-catenin independent) Wnt signaling pathways. Proliferation, differentiation, and even body-axis specification are carried out by the more well-known canonical pathway. This makes the Wnt signaling pathway a key factor in the development of many different diseases. Nonetheless, the diverse functions of the Wnt signaling pathway makes it a key area of research in therapeutics and treatments. While Wnt signaling has been studied for decades and numerous progresses have been made over the years, there is an unmet need to compile this information in a comprehensive fashion. In this issue, Yu M et al summarized our current knowledge of Wnts in stem cells, Wnt pathway-associated diseases, and pharmacologic targeting of the Wnt pathway (illustrated as the drummer), including both canonical ( ß-catenin dependent represented by drums on the right side) and/or noncanonical (PCP, Wnt/Ca⁺⁺ et al. represented by drums on the left side) (Illustration credit: Michael Yu, Kevin Qin, Huijie Zhang and Zijian Qu).