Long noncoding RNA SNHG16 silencing inhibits the aggressiveness of gastric cancer via upregulation of microRNA-628-3p and consequent decrease of NRP1
Authors Pang W, Zhai M, Wang Y, Li Z
Received 18 April 2019
Accepted for publication 5 July 2019
Published 1 August 2019 Volume 2019:11 Pages 7263—7277
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 2
Editor who approved publication: Dr Kenan Onel
Weifeng Pang,1 Mingcui Zhai,2 Yue Wang,3 Zhiqiang Li4
1Department of Internal Oncology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Department of Burn, Heilongjiang Province Hospital, Harbin, People’s Republic of China; 3Department of Pharmacology and Toxicology, Wright State University, Fairborn, OH, USA; 4Department of General Surgery, Suihua First Hospital in Heilongjiang Province, Suihua, People’s Republic of China
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, microRNA-628-3p, long noncoding RNA, neuropilin 1, small nucleolar RNA host gene 16
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