Article Abstract

Long non-coding RNA SNHG17 promotes gastric cancer progression by inhibiting P15 and P16

Authors: Cheng Gao, Xinqian Wu, Jing Zhai, Jiajia Shen, Shoulin Wang, Lizong Shen


Background: The dysregulated long non-coding RNA (lncRNA) small nucleolar RNA host genes (SNHGs) have been demonstrated to be involved in gastric carcinogenesis and progression; however, the role of SNHG17 in gastric carcinoma remains to be investigated. We aimed to ascertain the expression of SNHG17 in gastric carcinoma tissues and cell lines, and to investigate its mechanistic role in this malignancy.
Methods: The expression levels of SNHG17, P15, P16, P18, P19 and cyclin dependent kinases-4 (CDK4) were determined by real-time quantitative polymerase chain reaction (RT-qPCR) and/or western blotting in human gastric cancer tissues and cell lines. Correlations between SNHG17 levels and clinicopathological features were evaluated. siRNAs were used to silence SNHG17 in cell lines, and then Cell Counting Kit-8, colony formation, and transwell migration assays were used to assess proliferation, clonogenic potential, and migration, respectively. Flow cytometry was used to analyze cell cycle distributions and apoptosis. In vivo tumorigenicity was evaluated using xenografts in nude mice.
Results: Analysis of The Cancer Genome Atlas (TCGA) database revealed that SNHG17 expression was remarkably higher in gastric carcinoma tissues than normal stomach mucosae (P=4.85×10−10). We confirmed that SNHG17 was overexpressed in gastric cancer tissues (P<0.0001) and cell lines (P<0.01) compared with corresponding noncancerous tissues and gastric epithelial cell line, respectively. Furthermore, SNHG17 levels in tumor tissues were associated with lymph node metastasis (P=0.0006), pTNM stage (P=0.0061), and lymphovascular invasion (P=0.0005), but were not associated with overall survival (OS) (P=0.888). Loss-of-function studies indicated that SNHG17 promoted gastric carcinoma cell proliferation in vitro and in vivo (P<0.01), and that SNHG17 enhanced gastric cancer cell migration (P<0.01). Mechanistically, we found that SNHG17 inhibited P15 and P16, and enhanced CDK4 expression, resulting in a G0/G1 cell cycle arrest, and that SNHG17 inhibited cell apoptosis.
Conclusions: These preliminary findings highlight the role of SNHG17 in gastric cancer, and suggest that it may be a novel indicator and/or a potential therapeutic target for diagnosing and/or treating gastric cancer.

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