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Mutant ACTB mRNA 3'-UTR promotes hepatocellular carcinoma development by regulating miR-1 and miR-29a.
Cellular Signalling ( IF 4.4 ) Pub Date : 2019-12-14 , DOI: 10.1016/j.cellsig.2019.109479
Yong Li 1 , Hongbin Ma 1 , Changying Shi 2 , Feiling Feng 3 , Liang Yang 4
Affiliation  

In recent years, studies demonstrate that ACTB has been found to be associated with various tumors. Although ACTB is dysregulated in numerous cancer types, limited data are available on the potential function and mechanism of ACTB in hepatocellular carcinoma (HCC). This study evaluated the expression and biological roles of mutant ACTB mRNA 3'-UTR in HCC. Transcriptome sequence and qRT-PCR analysis determined that mutant ACTB mRNA '-UTR was high expression in tumor tissues. Luciferase reporter assay showed that the ACTB mRNA 3'-UTR mutations made it easier to interact with miR-1 and miR-29a. Moreover, mutant ACTB mRNA '-UTR regulated miR-1 and miR-29a degradation via AGO2. Furthermore, mutant ACTB mRNA 3'-UTR promoted hepatocellular carcinoma cells migration and invasion in vitro and in vivo by up-regulating miR-1 target gene MET and miR-29a target gene MCL1. In a word, our study demonstrates that 3'-UTR of ACTB plays a key role in the development of hepatocellular carcinoma (HCC) and highlights the molecular mechanisms underlying such a complex process.

中文翻译:

突变ACTB mRNA 3'-UTR通过调节miR-1和miR-29a促进肝细胞癌的发展。

近年来,研究表明,已经发现ACTB与各种肿瘤有关。尽管ACTB在许多癌症类型中失调,但关于ACTB在肝细胞癌(HCC)中的潜在功能和机制的可用数据有限。本研究评估了突变型ACTB mRNA 3'-UTR在肝癌中的表达及其生物学作用。转录组序列和qRT-PCR分析确定突变体ACTB mRNA'-UTR在肿瘤组织中高表达。萤光素酶报告基因检测表明ACTB mRNA 3'-UTR突变使与miR-1和miR-29a的相互作用更容易。此外,突变体ACTB mRNA'-UTR通过AGO2调节miR-1和miR-29a降解。此外,突变ACTB mRNA 3' -UTR通过上调miR-1靶基因MET和miR-29a靶基因MCL1促进肝癌细胞在体外和体内的迁移和侵袭。简而言之,我们的研究表明ACTB的3'-UTR在肝细胞癌(HCC)的发展中起着关键作用,并突显了这种复杂过程的分子机制。
更新日期:2019-12-17
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