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Circ‐MALAT1 Functions as Both an mRNA Translation Brake and a microRNA Sponge to Promote Self‐Renewal of Hepatocellular Cancer Stem Cells

Both circular RNAs (circRNAs) and cancer stem cells (CSCs) are separately known to be involved in cancer, but their interaction remains unclear. Here, the regulation of hepatocellular CSC self‐renewal is discovered by a circRNA, circ‐MALAT1, which is produced by back‐splicing of a long noncoding RNA...

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Autores principales: Chen, Liang, Kong, Ruijiao, Wu, Cong, Wang, Shuo, Liu, Zixin, Liu, Shupeng, Li, Shuiping, Chen, Tian, Mao, Chuanbin, Liu, Shanrong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029649/
https://www.ncbi.nlm.nih.gov/pubmed/32099751
http://dx.doi.org/10.1002/advs.201900949
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author Chen, Liang
Kong, Ruijiao
Wu, Cong
Wang, Shuo
Liu, Zixin
Liu, Shupeng
Li, Shuiping
Chen, Tian
Mao, Chuanbin
Liu, Shanrong
author_facet Chen, Liang
Kong, Ruijiao
Wu, Cong
Wang, Shuo
Liu, Zixin
Liu, Shupeng
Li, Shuiping
Chen, Tian
Mao, Chuanbin
Liu, Shanrong
author_sort Chen, Liang
collection PubMed
description Both circular RNAs (circRNAs) and cancer stem cells (CSCs) are separately known to be involved in cancer, but their interaction remains unclear. Here, the regulation of hepatocellular CSC self‐renewal is discovered by a circRNA, circ‐MALAT1, which is produced by back‐splicing of a long noncoding RNA, MALAT1. Circ‐MALAT1 is highly expressed in CSCs from clinical hepatocellular carcinoma samples under the mediation of an RNA‐binding protein, AUF1. Surprisingly, circMALAT1 functions as a brake in ribosomes to retard PAX5 mRNA translation and promote CSCs' self‐renewal by forming an unprecedented ternary complex with both ribosomes and mRNA. The discovered braking mechanism of a circRNA, termed mRNA braking, along with its more traditional role of miRNA sponging, uncovers a dual‐faceted pattern of circRNA‐mediated post‐transcriptional regulation for maintaining a specific cell state.
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spelling pubmed-70296492020-02-25 Circ‐MALAT1 Functions as Both an mRNA Translation Brake and a microRNA Sponge to Promote Self‐Renewal of Hepatocellular Cancer Stem Cells Chen, Liang Kong, Ruijiao Wu, Cong Wang, Shuo Liu, Zixin Liu, Shupeng Li, Shuiping Chen, Tian Mao, Chuanbin Liu, Shanrong Adv Sci (Weinh) Communications Both circular RNAs (circRNAs) and cancer stem cells (CSCs) are separately known to be involved in cancer, but their interaction remains unclear. Here, the regulation of hepatocellular CSC self‐renewal is discovered by a circRNA, circ‐MALAT1, which is produced by back‐splicing of a long noncoding RNA, MALAT1. Circ‐MALAT1 is highly expressed in CSCs from clinical hepatocellular carcinoma samples under the mediation of an RNA‐binding protein, AUF1. Surprisingly, circMALAT1 functions as a brake in ribosomes to retard PAX5 mRNA translation and promote CSCs' self‐renewal by forming an unprecedented ternary complex with both ribosomes and mRNA. The discovered braking mechanism of a circRNA, termed mRNA braking, along with its more traditional role of miRNA sponging, uncovers a dual‐faceted pattern of circRNA‐mediated post‐transcriptional regulation for maintaining a specific cell state. John Wiley and Sons Inc. 2019-12-21 /pmc/articles/PMC7029649/ /pubmed/32099751 http://dx.doi.org/10.1002/advs.201900949 Text en © 2019 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Communications
Chen, Liang
Kong, Ruijiao
Wu, Cong
Wang, Shuo
Liu, Zixin
Liu, Shupeng
Li, Shuiping
Chen, Tian
Mao, Chuanbin
Liu, Shanrong
Circ‐MALAT1 Functions as Both an mRNA Translation Brake and a microRNA Sponge to Promote Self‐Renewal of Hepatocellular Cancer Stem Cells
title Circ‐MALAT1 Functions as Both an mRNA Translation Brake and a microRNA Sponge to Promote Self‐Renewal of Hepatocellular Cancer Stem Cells
title_full Circ‐MALAT1 Functions as Both an mRNA Translation Brake and a microRNA Sponge to Promote Self‐Renewal of Hepatocellular Cancer Stem Cells
title_fullStr Circ‐MALAT1 Functions as Both an mRNA Translation Brake and a microRNA Sponge to Promote Self‐Renewal of Hepatocellular Cancer Stem Cells
title_full_unstemmed Circ‐MALAT1 Functions as Both an mRNA Translation Brake and a microRNA Sponge to Promote Self‐Renewal of Hepatocellular Cancer Stem Cells
title_short Circ‐MALAT1 Functions as Both an mRNA Translation Brake and a microRNA Sponge to Promote Self‐Renewal of Hepatocellular Cancer Stem Cells
title_sort circ‐malat1 functions as both an mrna translation brake and a microrna sponge to promote self‐renewal of hepatocellular cancer stem cells
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029649/
https://www.ncbi.nlm.nih.gov/pubmed/32099751
http://dx.doi.org/10.1002/advs.201900949
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