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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.

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.

SUBMITTER: Chen L

PROVIDER: S-EPMC7029649 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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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.

Chen Liang L Kong Ruijiao R Wu Cong C Wang Shuo S Liu Zixin Z Liu Shupeng S Li Shuiping S Chen Tian T Mao Chuanbin C Liu Shanrong S

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20191221 4

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 r ...[more]

PMID: 32099751

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Dataset Information

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

Publications

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

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