Department of Pathology, Infectious Diseases Institute, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Medical Oncology Institute, Hunan Cancer Hospital, Changsha, Hunan, China.
Invest New Drugs. 2020 Feb;38(1):60-69. doi: 10.1007/s10637-019-00766-8. Epub 2019 Mar 30.
MicroRNAs are involved in each stage of tumor development. Activation of the hepatocyte growth factor (HGF)/c-Met axis facilitates the proliferation and migration of cancer cells, and the HGF/c-MET pathway provides potential targets for anticancer treatment. However, the interaction between HGF and miRNAs in hepatocellular carcinoma (HCC) remains unknown. Previous studies have shown that miR-101 is downregulated in various types of cancer and acts as a tumor suppressor, but the role of miR-101 in HCC has not yet been well defined. Here, we show that HGF is upregulated while microRNA-101-3p is significantly downregulated in the tumor tissues of HCC. By combining bioinformatics analysis and luciferase reporter assays, we demonstrated that HGF is a direct target of miR-101. In vitro experiments indicated that miR-101 inhibits the migration and proliferation of HCC cells by targeting the HGF/c-MET axis, and in vivo studies showed that overexpressed miR-101 dramatically suppresses tumor growth. Therefore, the present study identifies miR-101 as a negative regulator of HGF/c-MET and suggests that miRNAs can be used as targeted drugs for the clinical treatment of HCC.
微小 RNA 参与肿瘤发展的各个阶段。肝细胞生长因子 (HGF)/c-Met 轴的激活促进癌细胞的增殖和迁移，HGF/c-MET 途径为抗癌治疗提供了潜在的靶点。然而，HGF 与肝癌 (HCC) 中的 miRNA 之间的相互作用尚不清楚。先前的研究表明，miR-101 在各种类型的癌症中下调，作为肿瘤抑制因子发挥作用，但 miR-101 在 HCC 中的作用尚未得到很好的定义。在这里，我们表明 HGF 在 HCC 的肿瘤组织中上调，而 microRNA-101-3p 则显著下调。通过结合生物信息学分析和荧光素酶报告基因检测，我们证明 HGF 是 miR-101 的直接靶标。体外实验表明，miR-101 通过靶向 HGF/c-MET 轴抑制 HCC 细胞的迁移和增殖，体内研究表明，过表达 miR-101 可显著抑制肿瘤生长。因此，本研究将 miR-101 鉴定为 HGF/c-MET 的负调节剂，并表明 miRNA 可作为 HCC 临床治疗的靶向药物。
