Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, P.R. China
Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, P.R. China.
Biosci Rep. 2019 May 15;39(5). doi: 10.1042/BSR20181823. Print 2019 May 31.
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 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.
蛋白酪氨酸磷酸酶 1B（PTP1B）已被报道为肝癌（HCC）中的癌基因。然而，PTP1B 在 HCC 中的调控机制尚不清楚。microRNAs（miRNAs）是一类参与包括肿瘤发生在内的许多生物学过程的小非编码 RNA。在本研究中，我们研究了 miRNA 是否参与 HCC 中 PTP1B 的调控。我们发现，miR-206 在肿瘤发生过程中下调，抑制 HCC 细胞增殖和侵袭。miR-206 的过表达抑制 HCC 细胞系 HepG2 和 Huh7 的增殖、侵袭和迁移。通过荧光素酶报告基因检测证实，miR-206 通过与 PTP1B mRNA 的 3'-UTR 结合，直接靶向 PTP1B。miR-206 的过表达抑制了 HepG2 和 Huh7 细胞中 PTP1B 的表达，而 miR-206 的抑制增强了 PTP1B 的表达。功能上，miR-206 对细胞增殖/迁移/侵袭的调节作用可被 PTP1B 的过表达逆转。此外，我们还使用肿瘤接种裸鼠模型来探讨 miR-206 的功能。我们的结果表明，miR-206 的过表达可显著抑制肿瘤的发展。综上所述，我们的数据表明，miR-206 通过靶向 PTP1B 抑制 HCC 的发展。
