MiR-887 Promotes the Progression of Hepatocellular Carcinoma via Targeting VHL

Abstract

Background: MiR-887 has been proved to promote the tumorigenesis in diverse cancers, but its function and downstream mechanism in hepatocellular carcinoma remain obscure. Methods: Quantitative real-time polymerase chain reaction was performed to detect the expression levels of miR-887 in hepatocellular carcinoma tissues and cell lines. MiR-887 mimics and miR-887 inhibitor were transfected into Huh7 and MHCC97H to establish miR-887 overexpression or inhibition models. Cell Counting Kit-8 and colony formation experiment were conducted to monitor cell proliferation. Subcutaneous xenotransplanted tumor model and tail vein injection model in mice were also established to further verify the effect of miR-887 on hepatocellular carcinoma in vivo. The targeting relationship between miR-887 and von Hippel-Lindau tumor suppressor (VHL) was determined by quantitative real-time polymerase chain reaction, Western blot, and luciferase reporter gene assay. Results: miR-887 expression in hepatocellular carcinoma tissues was significantly upregulated. Compared with the control cells, the proliferation and metastasis of cancer cells were enhanced by miR-887 mimics and suppressed by miR-887 inhibitor. Compared with control mice, the volume and weight of subcutaneous tumors of mice in the miR-887 mimics group were significantly elevated, and the significant increase was found in the occurrence of lung metastasis. Moreover, bioinformatics tools showed that miR-887 and VHL had 2 binding sites. Luciferase activity assay demonstrated that miR-887 can inhibit the luciferase activity of VHL, and miR-887 mimics could reduce the expressions of VHL at both messenger RNA and protein levels to increase hypoxia-inducible factor α expression. Conclusion: The upregulation of miR-887 could facilitate the proliferation and metastasis of hepatocellular carcinoma cells via targeting VHL.