Department of Intervention Radiology, Zhongshan Hospital of Fudan University, No. 180 Fenglin Road, Xuhui, Shanghai 20032, China..
Gene. 2018 Jun 15;659:22-28. doi: 10.1016/j.gene.2018.03.053. Epub 2018 Mar 17.
Hepatocellular carcinoma (HCC), the most common primary tumor of the liver, has a poor prognosis and shows rapid progression. MicroRNAs (miRNAs) play important roles in carcinogenesis and tumor progression. Regulators of G-protein signaling (RGS) are critical for defining G-protein-dependent signal fidelity. RGS17 plays an important role in the regulation of cancer cell proliferation, migration and invasion. Here, we showed that miR-199 was downregulated in a hepatocarcinoma cell line. Overexpression of miR-199 significantly suppressed HCC cell proliferation, migration, and invasion in vitro. RGS17 overexpression promoted HCC cell proliferation, migration, and invasion, and reversed the miR-199 mediated inhibition of proliferation, migration, and invasion. Dual-fluorescence reporter experiments confirmed that miR-199 downregulated RGS17 by direct interaction with the 3'-UTR of RGS17 mRNA. In vivo studies showed that miR-199 overexpression significantly inhibited the growth of tumors. Taken together, the results suggested that miR-199 inhibited tumor growth and metastasis by targeting RGS17.
肝细胞癌（HCC）是肝脏最常见的原发性肿瘤，预后不良，且进展迅速。微小 RNA（miRNA）在致癌作用和肿瘤进展中发挥重要作用。G 蛋白信号转导调节因子（RGS）对于定义 G 蛋白依赖性信号保真度至关重要。RGS17 在调节癌细胞增殖、迁移和侵袭中发挥重要作用。在这里，我们发现 miR-199 在肝癌细胞系中下调。miR-199 的过表达显著抑制 HCC 细胞在体外的增殖、迁移和侵袭。RGS17 的过表达促进 HCC 细胞的增殖、迁移和侵袭，并逆转了 miR-199 介导的对增殖、迁移和侵袭的抑制。双荧光素酶报告实验证实 miR-199 通过与 RGS17 mRNA 的 3'-UTR 直接相互作用下调 RGS17。体内研究表明，miR-199 的过表达显著抑制了肿瘤的生长。综上所述，这些结果表明 miR-199 通过靶向 RGS17 抑制肿瘤生长和转移。
