SNHG16 facilitates proliferation and migration of hepatocellular carcinoma cells by Wnt/β-catenin signaling pathway / 肿瘤

ABSTRACT

Objective: To investigate the expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 16 (SNHG16) in hepatocellular carcinoma (HCC) tissues and cells, and to explore the effects of SNHG16 expression regulation on the proliferation and migration of HCC cells as well as the underlying molecular mechanisms. Methods: The cancer tissues and adjacent tissues were collected from 38 patients with HCC. The real-time fluorescent quantitative PCR was used to detected the expression of SNHG16 in 38 cases of clinical HCC tissue samples and their adjacent tissues, 4 kinds of HCC cell lines and normal hepatocellular cell line. The relationship between SNHG16 expression and the clinicopathological features of HCC patients was analyzed. The SNHG16 overexpression or SNHG16-shRNA recombinant lentivirus was infected into Hep-3B or SK-Hep-1 cells, respectively. The up- or down-regulation of SNHG16 expression in Hep-3B or SK-Hep-1 cells was verified by real-time fluorescent quantitative PCR. The effects of SNHG16 expression regulation on the proliferation and migration of HCC cells were determined by CCK-8 and Transwell chamber experiments, respectively. The expressions of key proteins in Wnt/β-catenin signaling pathway were detected by Western blotting. Xenograft tumor experiment was used to determine the effect of SNHG16 on the tumorigenic ability of HCC cells in nude mice. Results: The expression level of SNHG16 in HCC tissues and HCC cells was significantly higher than that in the adjacent tissues (P < 0.001) and normal hepatocellular cells (P < 0.05), respectively. The expression of SNHG16 in HCC tissues was associated with tumor size (P < 0.01), TNM stage (P < 0.01) and alanine aminotransaminase (ALT) expression level (P < 0.05). After the infection with SNHG16 overexpression recombinant lentivirus, the expression of SNHG16 was significantly up-regulated in Hep-3B cells (P < 0.001), the proliferation and migration of Hep-3B cells were significantly promoted (both P < 0.01), and the expressions of β-catenin and c-myc proteins were up-regulated (both P < 0.01). After the infection with SNHG16-shRNA recombinant lentivirus, the expression of SNHG16 was dramatically downregulated in SK-Hep-1 cells (P < 0.001), the proliferation and migration of SK-Hep-1 cells were significantly inhibited (both P < 0.001), and the expressions of β-catenin (P < 0.05) and c-myc (P < 0.01) proteins were down-regulated. In addition, the tumorigenic ability of Hep- 3B cells with SNHG16 over-expression was significantly enhanced in nude mice (P < 0.01), while the tumorigenic ability of SK-Hep-1 cells with SNHG16 knock-down was significantly weakened in nude mice (P < 0.05). Conclusion: SNHG16 is highly expressed in HCC tissues and cell lines, and may promote the proliferation and migration of HCC cells through Wnt/β-catenin signaling pathway.