Open AccessCirc‐MALAT1 Functions as Both an mRNA Translation Brake and a microRNA Sponge to Promote Self‐Renewal of Hepatocellular Cancer Stem Cells
Author(s) -
Chen Liang,
Kong Ruijiao,
Wu Cong,
Wang Shuo,
Liu Zixin,
Liu Shupeng,
Li Shuiping,
Chen Tian,
Mao Chuanbin,
Liu Shanrong
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201900949
Subject(s) - microrna , messenger rna , translation (biology) , biology , microbiology and biotechnology , rna , cancer stem cell , gene silencing , malat1 , stem cell , long non coding rna , cancer research , chemistry , gene , genetics
Abstract 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.