Circ-MALAT1 Functions as Both an mRNA Translation Brake and a microRNA Sponge to Promote Self-Renewal of Hepatocellular Cancer Stem Cells
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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Circ-MALAT1 既作为 mRNA 翻译制动器又作为 microRNA 海绵，促进肝细胞癌干细胞的自我更新
DOI：
10.1002/advs.201900949
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发表时间：
2019-12-21
期刊：
影响因子：
15.1
通讯作者：
Liu, Shanrong
中科院分区：
文献类型：
--
作者：
Chen, Liang;Kong, Ruijiao;Liu, Shanrong
已知环状RNA（circRNA）和癌症干细胞（CSC）分别参与癌症，但它们的相互作用仍不清楚。在这里，肝细胞CSC自我更新的调节是由circRNA，circ-MALAT 1发现的，它是由长的非编码RNA，MALAT 1的反向剪接产生的。Circ-MALAT 1在来自临床肝细胞癌样品的CSC中在RNA结合蛋白AUF 1的介导下高度表达。令人惊讶的是，circMALAT 1在核糖体中起制动器的作用，以通过与核糖体和mRNA形成前所未有的三元复合物来延迟PAX 5 mRNA翻译并促进CSC的自我更新。已发现的circRNA的制动机制（称为mRNA制动）及其更传统的miRNA海绵作用（沿着）揭示了circRNA介导的转录后调节的双重模式，以维持特定的细胞状态。
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.