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miR-206 inhibits cell proliferation invasion and migration by down-regulating PTP1B in hepatocellular carcinoma

机译:miR-206通过下调肝细胞癌中的PTP1B抑制细胞增殖侵袭和迁移

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摘要

Protein tyrosine phosphatase 1B (PTP1B) has been reported as an oncogene in hepatocellular carcinoma (HCC). However, how PTP1B is regulated in HCC remains unclear. MicroRNAs (miRNAs) are a class of small non-coding RNAs involved many biological processes including tumorigenesis. In this study, we investigated whether miRNA participated in the regulation of PTP1B in HCC. We found that miR-206, which was down-regulated during tumorigenesis, inhibited HCC cell proliferation and invasion. Overexpression of miR-206 inhibited proliferation, invasion, and migration of HCC cell lines HepG2 and Huh7. Mechanistically, we demonstrated that miR-206 directly targeted PTP1B by binding to the 3′-UTR of PTP1B mRNA as demonstrated by the luciferase reporter assay. Overexpression miR-206 inhibited PTP1B expression while miR-206 inhibition enhanced PTP1B expression in HepG2 and Huh7 cells. Functionally, the regulatory effect on cell proliferation/migration/invasion of miR-206 was reversed by PTP1B overexpression. Furthermore, tumor inoculation nude mice model was used to explore the function of miR-206 in vivo. Our results showed that overexpression of miR-206 drastically inhibited tumor development. In summary, our data suggest that miR-206 inhibits HCC development by targeting PTP1B.
机译:据报道,蛋白酪氨酸磷酸酶1B(PTP1B)是肝细胞癌(HCC)的致癌基因。但是,如何在HCC中调节PTP1B尚不清楚。微小RNA(miRNA)是一类小的非编码RNA,涉及许多生物过程,包括肿瘤发生。在这项研究中,我们调查了miRNA是否参与了HCC中PTP1B的调控。我们发现,在肿瘤发生过程中被下调的miR-206抑制了HCC细胞的增殖和侵袭。 miR-206的过表达抑制了HCC细胞系HepG2和Huh7的增殖,侵袭和迁移。从机制上讲,我们证明了miR-206通过与PTP1B mRNA的3'-UTR结合而直接靶向PTP1B,如荧光素酶报告基因检测所证实的那样。在HepG2和Huh7细胞中,miR-206的过表达抑制了PTP1B的表达,而miR-206的抑制则增强了PTP1B的表达。在功能上,PTP1B过表达逆转了对miR-206细胞增殖/迁移/侵袭的调控作用。此外,使用肿瘤接种裸鼠模型探索miR-206在体内的功能。我们的结果表明,miR-206的过度表达可显着抑制肿瘤的发展。总之,我们的数据表明miR-206通过靶向PTP1B抑制HCC的发展。

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