Long noncoding RNA SNHG16 silencing inhibits the aggressiveness of gastric cancer via upregulation of microRNA-628-3p and consequent decrease of NRP1

Cancer Manag Res. 2019 Aug 1;11:7263-7277. doi: 10.2147/CMAR.S211856. eCollection 2019.

Abstract

Background: MicroRNA-628-3p (miR-628) has been reported to play important roles in the progression of multiple human cancer types. Nonetheless, whether the expression profile of miR-628 is altered in gastric cancer remains unclear and whether its aberrant expression plays a crucial part in the aggressiveness of gastric cancer is yet to be determined. Therefore, in this study, we systematically investigated the involvement of miR-628 in gastric cancer progression.

Materials and methods: MiR-628 expression in gastric cancer tissues and cell lines were determined via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A CCK-8 assay, flow-cytometric analysis, Transwell assays, and a xenograft model experiment were performed to evaluate the influence of miR-628 overexpression on gastric cancer cells. Notably, the mechanisms underlying the tumor-suppressive activity of miR-628 in gastric cancer cells were explored by bioinformatics analysis, a luciferase reporter assay, RT-qPCR, and Western blotting.

Results: MiR-628 expression was low in gastric cancer tissue samples and cell lines. The low expression of miR-628 was closely associated with the lymph node metastasis, invasive depth and TNM stage among patients with gastric cancer. Further clinical analysis indicated that patients with gastric cancer underexpressing miR-628 had a worse prognosis than did the patients with high miR-628 expression in the tumor. Overexpressed miR-628 restrained proliferation, migration, and invasion; induced apoptosis; and impaired tumor growth of gastric cancer cells. In addition, neuropilin 1 (NRP1) mRNA was validated as the direct target of miR-628 in gastric cancer. Long noncoding RNA small nucleolar RNA host gene 16 (SNHG16) was demonstrated to sponge miR-628 in gastric cancer. Moreover, miR-628 knockdown abrogated the influence of SNHG16 silencing on gastric cancer cells.

Conclusion: Our findings elucidate how the SNHG16-miR-628-NRP1 pathway serves as a regulatory network playing crucial roles in gastric cancer progression, suggesting that this pathway may be a novel target of anticancer therapy.

Keywords: gastric cancer; long noncoding RNA; microRNA-628-3p; neuropilin 1; small nucleolar RNA host gene 16.