Yang Zhan-Po, Ma Hong-Shun, Wang Shu-Sen, Wang Le, Liu Tao
Department of Urology, Tianjin First Central Hospital, Tianjin, China.
Key Laboratory for Critical Care Medicine of the Ministry of Health, Tianjin First Central Hospital, Tianjin, China.
IUBMB Life. 2017 Aug;69(8):595-605. doi: 10.1002/iub.1642. Epub 2017 May 19.
Specific RNAs can function as sinks for endogenous miRNAs, known as competing endogenous RNAs (ceRNAs). Here, we confirm a miR-124 mediated ceRNA crosstalk between LAMC1 and CD151 in hepatocellular carcinoma (HCC). miR-124 negatively regulates LAMC1 expression through two miRNA binding sites within its 3' untranslated region (3'UTR) and suppresses migration and invasion of HCC cells through regulating LAMC1. The wild type LAMC1 miRNA response elements (MREs) facilitate expression of CD151, and this regulation is miR-124 dependent. In clinical hepatic tissues, LAMC1 and CD151 mRNAs exhibit positive correlation. Importantly, LAMC1 MREs promote HCC malignancy by absorbing miR-124 and by assisting CD151 expression. We conclude that LAMC1 mRNA acts as a trans regulator to stimulate CD151 expression by competing for miR-124 binding in HCC cells. © 2017 IUBMB Life, 69(8):595-605, 2017.
特定的RNA可作为内源性miRNA的“海绵”,即竞争性内源性RNA(ceRNA)。在此,我们证实了在肝细胞癌(HCC)中miR-124介导的LAMC1与CD151之间的ceRNA串扰。miR-124通过其3'非翻译区(3'UTR)内的两个miRNA结合位点负向调节LAMC1的表达,并通过调节LAMC1抑制HCC细胞的迁移和侵袭。野生型LAMC1的miRNA反应元件(MRE)促进CD151的表达,且这种调节依赖于miR-124。在临床肝脏组织中,LAMC1和CD151 mRNA呈正相关。重要的是,LAMC1的MRE通过吸附miR-124并辅助CD151表达来促进HCC的恶性进展。我们得出结论,在HCC细胞中,LAMC1 mRNA通过竞争结合miR-124作为反式调节因子刺激CD151的表达。©2017国际生物化学与分子生物学联盟生命科学,69(8):595 - 605, 2017。