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一种新型长链非编码 RNA MTAR1 通过 IGF2BPs 介导的 c-MYC 转录后调控促进癌症发展。

A novel lncRNA MTAR1 promotes cancer development through IGF2BPs mediated post-transcriptional regulation of c-MYC.

机构信息

China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450000, China.

Pathophysiology Department, The School of Basic Medical Sciences, AMS, Zhengzhou University, Zhengzhou, 450000, China.

出版信息

Oncogene. 2022 Oct;41(42):4736-4753. doi: 10.1038/s41388-022-02464-x. Epub 2022 Sep 15.

Abstract

Abnormal translation of the MYC proto-oncogene is a hallmark of the initiation and maintenance of tumorigenesis. However, the molecular mechanism underlying increased MYC protein levels in certain cancer types without a corresponding increase in MYC mRNA levels is unclear. Here, we identified a novel lncRNA, MTAR1, which is critical for post-transcriptional regulation of MYC-induced tumorigenesis. MTAR1 is essential for recruiting IGF2BPs into PABP1-mediated liquid-liquid phase separation (LLPS) complexes and facilitates IGF2BPs-mediated MYC mRNA translation. MTAR1 enhanced binding between IGF2BPs and PABP1, thereby promoting MYC mRNA stability and increased MYC mRNA translation. In summary, MTAR1 is a novel MYC-related lncRNA that contributes to tumor progression by enhancing MYC translation through mediating PABP1/IGF2BPs liquid-liquid phase separation.

摘要

MYC 原癌基因的异常翻译是肿瘤发生起始和维持的标志。然而,在某些癌症类型中,MYC 蛋白水平的增加而 MYC mRNA 水平没有相应增加的分子机制尚不清楚。在这里,我们鉴定了一种新的长非编码 RNA(lncRNA)MTAR1,它对于 MYC 诱导的肿瘤发生的转录后调控至关重要。MTAR1 对于将 IGF2BPs 募集到 PABP1 介导的液-液相分离(LLPS)复合物中是必需的,并且促进 IGF2BPs 介导的 MYC mRNA 翻译。MTAR1 增强了 IGF2BPs 和 PABP1 之间的结合,从而促进了 MYC mRNA 的稳定性和增加了 MYC mRNA 的翻译。总之,MTAR1 是一种新型的 MYC 相关 lncRNA,通过介导 PABP1/IGF2BPs 液-液相分离来增强 MYC 翻译,从而促进肿瘤进展。

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