For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
6
views
35
references
 Top references
cited by
27
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      243
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Transcriptional factor six2 promotes the competitive endogenous RNA network between CYP4Z1 and pseudogene CYP4Z2P responsible for maintaining the stemness of breast cancer cells

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          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

          Background

          The expression of CYP4Z1 and the pseudogene CYP4Z2P has been shown to be specifically increased in breast cancer by our group and others. Additionally, we previously revealed the roles of the competitive endogenous RNA (ceRNA) network mediated by these genes (ceRNET_CC) in breast cancer angiogenesis, apoptosis, and tamoxifen resistance. However, the roles of ceRNET_CC in regulating the stemness of breast cancer cells and the mechanisms through which ceRNET_CC is regulated remain unclear.

          Methods

          Transcriptional factor six2, CYP4Z1-3′UTR, and CYP4Z2P-3′UTR were stably overexpressed or knocked down in breast cancer cells via lentivirus infection. ChIP-sequencing and RNA-sequencing analysis were performed to reveal the mechanism through which ceRNET_CC is regulated and the transcriptome change mediated by ceRNET_CC. Clinical samples were used to validate the correlation between six2 and ceRNET_CC. Finally, the effects of the six2/ceRNET_CC axis on the stemness of breast cancer cells and chemotherapy sensitivity were evaluated by in vitro and in vivo experiments.

          Results

          We revealed that ceRNET_CC promoted the stemness of breast cancer cells. Mechanistically, six2 activated ceRNET_CC by directly binding to their promoters, thus activating the downstream PI3K/Akt and ERK1/2 pathways. Finally, we demonstrated that the six2/ceRNET_CC axis was involved in chemoresistance.

          Conclusions

          Our results uncover the mechanism through which ceRNET_CC is regulated, identify novel roles for the six2/ceRNET_CC axis in regulating the stemness of breast cancer cells, and propose the possibility of targeting the six2/ceRNET_CC axis to inhibit breast cancer stem cell (CSC) traits.

          Electronic supplementary material

          The online version of this article (10.1186/s13045-019-0697-6) contains supplementary material, which is available to authorized users.

          Related collections

          Most cited references35

          • Record: found
          • Abstract: found
          • Article: not found

          miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients.

          András Lánczky, Ádám Nagy, Giulia Bottai … (2016)
          The proper validation of prognostic biomarkers is an important clinical issue in breast cancer research. MicroRNAs (miRNAs) have emerged as a new class of promising breast cancer biomarkers. In the present work, we developed an integrated online bioinformatic tool to validate the prognostic relevance of miRNAs in breast cancer.
          Article 0 comments Cited 427 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development.

            Akio Kobayashi, M Todd Valerius, Joshua Mugford … (2008)
            Nephrons, the basic functional units of the kidney, are generated repetitively during kidney organogenesis from a mesenchymal progenitor population. Which cells within this pool give rise to nephrons and how multiple nephron lineages form during this protracted developmental process are unclear. We demonstrate that the Six2-expressing cap mesenchyme represents a multipotent nephron progenitor population. Six2-expressing cells give rise to all cell types of the main body of the nephron during all stages of nephrogenesis. Pulse labeling of Six2-expressing nephron progenitors at the onset of kidney development suggests that the Six2-expressing population is maintained by self-renewal. Clonal analysis indicates that at least some Six2-expressing cells are multipotent, contributing to multiple domains of the nephron. Furthermore, Six2 functions cell autonomously to maintain a progenitor cell status, as cap mesenchyme cells lacking Six2 activity contribute to ectopic nephron tubules, a mechanism dependent on a Wnt9b inductive signal. Taken together, our observations suggest that Six2 activity cell-autonomously regulates a multipotent nephron progenitor population.
            Article 0 comments Cited 281 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Module map of stem cell genes guides creation of epithelial cancer stem cells.

              David J. Wong, Helen Liu, Todd W Ridky … (2008)
              Self-renewal is a hallmark of stem cells and cancer, but existence of a shared stemness program remains controversial. Here, we construct a gene module map to systematically relate transcriptional programs in embryonic stem cells (ESCs), adult tissue stem cells, and human cancers. This map reveals two predominant gene modules that distinguish ESCs and adult tissue stem cells. The ESC-like transcriptional program is activated in diverse human epithelial cancers and strongly predicts metastasis and death. c-Myc, but not other oncogenes, is sufficient to reactivate the ESC-like program in normal and cancer cells. In primary human keratinocytes transformed by Ras and I kappa B alpha, c-Myc increases the fraction of tumor-initiating cells by 150-fold, enabling tumor formation and serial propagation with as few as 500 cells. c-Myc-enhanced tumor initiation is cell-autonomous and independent of genomic instability. Thus, activation of an ESC-like transcriptional program in differentiated adult cells may induce pathologic self-renewal characteristic of cancer stem cells.
              Article 0 comments Cited 246 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Lufeng Zheng: zhlf@cpu.edu.cn
                Qianqian Guo: 545948829@qq.com
                Chenxi Xiang: 1017317643@qq.com
                Shijia Liu: liushijia2011@163.com
                Yuzhang Jiang: 13861579633@126.com
                Lanlan Gao: langaoing@qq.com
                Haiwei Ni: 1452342935@qq.com
                Ting Wang: 331663123@qq.com
                Qiong Zhao: 2649406210@qq.com
                Hai Liu: 381733818@qq.com
                Yingying Xing: 111840@qq.com
                Yaohui Wang: 13861579633@126.com
                Xiaoman Li: + 86 25 8327 1022 , xiaoman1205@163.com
                Tao Xi:
                ORCID: https://orcid.org/0000-0001-8065-2639
                + 86 25 8327 1022 , xitao18@hotmail.com
                Journal
                Journal ID (nlm-ta): J Hematol Oncol
                Journal ID (iso-abbrev): J Hematol Oncol
                Title: Journal of Hematology & Oncology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1756-8722
                Publication date (Electronic): 4 March 2019
                Publication date PMC-release: 4 March 2019
                Publication date Collection: 2019
                Volume: 12
                Electronic Location Identifier: 23
                Affiliations
                [1 ]ISNI 0000 0000 9776 7793, GRID grid.254147.1, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Life Science and Technology, , China Pharmaceutical University, ; 24 Tong Jia Xiang, Nanjing, 210009 China
                [2 ]ISNI 0000 0004 1765 1045, GRID grid.410745.3, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, , Nanjing University of Chinese Medicine, ; Nanjing, 210023 China
                [3 ]GRID grid.413389.4, Department of Pathology, , The Affiliated Hospital of Xuzhou Medical University, ; Xuzhou, 221002 Jiangsu China
                [4 ]ISNI 0000 0004 1790 425X, GRID grid.452524.0, Department of Pharmacy, , Jiangsu Province Hospital of TCM, ; Nanjing, 210023 China
                [5 ]Department of Clinical Laboratory, Huai An First People’s Hospital, Huai An, 223300 China
                [6 ]ISNI 0000 0004 1790 425X, GRID grid.452524.0, Department of Pathology, , Jiangsu Province Hospital of TCM, ; Nanjing, 210023 China
                Author information
                https://orcid.org/0000-0001-8065-2639
                Article
                Publisher ID: 697
                DOI: 10.1186/s13045-019-0697-6
                PMC ID: 6399913
                PubMed ID: 30832689
                SO-VID: ca57ab65-9ff6-4688-8707-d8da4e189241
                Copyright © © The Author(s). 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.

                History
                Date received : 30 September 2018
                Date accepted : 13 January 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: No. 81702957
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100010031, Postdoctoral Research Foundation of China;
                Award ID: No.2017M620230
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100010246, Postdoctoral Science Foundation of Jiangsu Province;
                Award ID: No.1701197B
                Award Recipient :
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cyp4z1,pseudogene cyp4z2p,cernet_cc,six2,stemness,chemoresistance,breast cancer
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cyp4z1, pseudogene cyp4z2p, cernet_cc, six2, stemness, chemoresistance, breast cancer

                Comments

                Comment on this article

                scite_

                Similar content243

                See all similar

                Cited by27

                See all cited by

                Most referenced authors869

                See all reference authors