The role of long noncoding RNAs in hepatocellular carcinoma

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Hepatocellular carcinoma (HCC) is the most frequent subtype of primary liver cancer and one of the leading causes of cancer-related death worldwide. However, the molecular mechanisms underlying HCC pathogenesis have not been fully understood. Emerging evidences have recently suggested the crucial role of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of HCC. Various HCC-related lncRNAs have been shown to possess aberrant expression and participate in cancerous phenotypes (e.g. persistent proliferation, evading apoptosis, accelerated vessel formation and gain of invasive capability) through their binding with DNA, RNA or proteins, or encoding small peptides. Thus, a deeper understanding of lncRNA dysregulation would provide new insights into HCC pathogenesis and novel tools for the early diagnosis and treatment of HCC. In this review, we summarize the dysregulation of lncRNAs expression in HCC and their tumor suppressive or oncogenic roles during HCC tumorigenesis. Moreover, we discuss the diagnostic and therapeutic potentials of lncRNAs in HCC.

Related collections

Most cited references 86

Record: found
Abstract: found
Article: not found

Long noncoding RNA as modular scaffold of histone modification complexes.

Miao-Chih Tsai, Ohad Manor, Yue Wan … (2010)

Long intergenic noncoding RNAs (lincRNAs) regulate chromatin states and epigenetic inheritance. Here, we show that the lincRNA HOTAIR serves as a scaffold for at least two distinct histone modification complexes. A 5' domain of HOTAIR binds polycomb repressive complex 2 (PRC2), whereas a 3' domain of HOTAIR binds the LSD1/CoREST/REST complex. The ability to tether two distinct complexes enables RNA-mediated assembly of PRC2 and LSD1 and coordinates targeting of PRC2 and LSD1 to chromatin for coupled histone H3 lysine 27 methylation and lysine 4 demethylation. Our results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.

0 comments Cited 1277 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma

(2017)

Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole exome sequencing and DNA copy number analyses, and 196 HCC also by DNA methylation, RNA, miRNA, and proteomic expression. DNA sequencing and mutation analysis identified significantly mutated genes including LZTR1 , EEF1A1 , SF3B1 , and SMARCA4 . Significant alterations by mutation or down-regulation by hypermethylation in genes likely to result in HCC metabolic reprogramming ( ALB , APOB , and CPS1 ) were observed. Integrative molecular HCC subtyping incorporating unsupervised clustering of five data platforms identified three subtypes, one of which was associated with poorer prognosis in three HCC cohorts. Integrated analyses enabled development of a p53 target gene expression signature correlating with poor survival. Potential therapeutic targets for which inhibitors exist include WNT signaling, MDM4, MET, VEGFA, MCL1, IDH1, TERT, and immune checkpoint proteins CTLA-4, PD-1, and PD-L1. Multiplex molecular profiling of human hepatocellular carcinoma patients provides insight into subtype characteristics and points toward key pathways to target therapeutically.

0 comments Cited 914 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The evolution of lncRNA repertoires and expression patterns in tetrapods.

Anamaria Necsulea, Magali Soumillon, Maria Warnefors … (2014)

Only a very small fraction of long noncoding RNAs (lncRNAs) are well characterized. The evolutionary history of lncRNAs can provide insights into their functionality, but the absence of lncRNA annotations in non-model organisms has precluded comparative analyses. Here we present a large-scale evolutionary study of lncRNA repertoires and expression patterns, in 11 tetrapod species. We identify approximately 11,000 primate-specific lncRNAs and 2,500 highly conserved lncRNAs, including approximately 400 genes that are likely to have originated more than 300 million years ago. We find that lncRNAs, in particular ancient ones, are in general actively regulated and may function predominantly in embryonic development. Most lncRNAs evolve rapidly in terms of sequence and expression levels, but tissue specificities are often conserved. We compared expression patterns of homologous lncRNA and protein-coding families across tetrapods to reconstruct an evolutionarily conserved co-expression network. This network suggests potential functions for lncRNAs in fundamental processes such as spermatogenesis and synaptic transmission, but also in more specific mechanisms such as placenta development through microRNA production.

0 comments Cited 450 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Zhao Huang: 472863779@qq.com

Jian-Kang Zhou: zhoujiankang@scu.edu.cn

Yong Peng: yongpeng@scu.edu.cn

Weifeng He: whe761211@hotmail.com

Canhua Huang: hcanhua@hotmail.com

Journal

Journal ID (nlm-ta): Mol Cancer

Journal ID (iso-abbrev): Mol. Cancer

Title: Molecular Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1476-4598

Publication date (Electronic): 15 April 2020

Publication date PMC-release: 15 April 2020

Publication date Collection: 2020

Volume: 19

Electronic Location Identifier: 77

Affiliations

[1 ]GRID grid.13291.38, ISNI 0000 0001 0807 1581, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, , Sichuan University, and Collaborative Innovation Center for Biotherapy, ; Chengdu, 610041 China

[2 ]GRID grid.416208.9, ISNI 0000 0004 1757 2259, Institute of Burn Research, Southwest Hospital; State Key Laboratory of Trauma, Burn and Combined Injury, , Chongqing Key Laboratory for Disease Proteomics, Army Military Medical University, ; Chongqing, 400038 China

Article

Publisher ID: 1188

DOI: 10.1186/s12943-020-01188-4

PMC ID: 7161154

PubMed ID: 32295598

SO-VID: 96558b35-85c4-45ba-8f31-74fa55a8b5aa

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 1 January 2020

Date accepted : 19 March 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 81821002, 81790251, 81430071 and 81672381

Award Recipient : Canhua Huang

Funded by: Guangdong Basic and Applied Basic Research Foundation

Award ID: 2019B030302012

Award Recipient : Canhua Huang

Funded by: FundRef http://dx.doi.org/10.13039/501100012166, National Basic Research Program of China (973 Program);

Award ID: 2013CB911300

Award Recipient : Canhua Huang

Funded by: FundRef http://dx.doi.org/10.13039/501100004829, Department of Science and Technology of Sichuan Province;

Award ID: 2019JDTD0013

Award Recipient : Yong Peng

Funded by: The 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University

Award ID: ZYJC18030

Award Recipient : Yong Peng

Funded by: FundRef http://dx.doi.org/10.13039/501100012226, Fundamental Research Funds for the Central Universities;

Award ID: 2018SCUH0018

Award Recipient : Yong Peng

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: long noncoding rna,hepatocellular carcinoma,biomarker,targeted therapy

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: long noncoding rna, hepatocellular carcinoma, biomarker, targeted therapy

The role of long noncoding RNAs in hepatocellular carcinoma

Read this article at

Abstract

Related collections

Karger: Oncology

Most cited references 86

Long noncoding RNA as modular scaffold of histone modification complexes.

Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma

The evolution of lncRNA repertoires and expression patterns in tetrapods.

Author and article information

Contributors

Journal

Affiliations

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 1,262

Cited by 212

Most referenced authors 4,310