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

• Published in: Translational cancer research Vol. 8; no. 2; pp. 520 - 531
• Main Authors: Gao, Cheng, Wu, Xinqian, Zhai, Jing, Shen, Jiajia, Wang, Shoulin, Shen, Lizong
• Format: Journal Article
• Language: English
• Published: China AME Publishing Company 01.04.2019
• Subjects: Original; migration; apoptosis; proliferation; cell cycle; Gastric cancer; small nucleolar RNA host genes (SNHGs)
• ISSN: 2218-676X; 2219-6803; 2219-6803
• DOI: 10.21037/tcr.2019.04.14

The dysregulated long non-coding RNA (lncRNA) small nucleolar RNA host genes ( ) have been demonstrated to be involved in gastric carcinogenesis and progression; however, the role of in gastric carcinoma remains to be investigated. We aimed to ascertain the expression of in gastric carcinoma tissues and cell lines, and to investigate its mechanistic role in this malignancy. The expression levels of , , , , 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 levels and clinicopathological features were evaluated. siRNAs were used to silence 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. tumorigenicity was evaluated using xenografts in nude mice. Analysis of The Cancer Genome Atlas (TCGA) database revealed that expression was remarkably higher in gastric carcinoma tissues than normal stomach mucosae (P=4.85×10 ). We confirmed that 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, 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 promoted gastric carcinoma cell proliferation and (P<0.01), and that enhanced gastric cancer cell migration (P<0.01). Mechanistically, we found that inhibited and , and enhanced CDK4 expression, resulting in a G0/G1 cell cycle arrest, and that inhibited cell apoptosis. These preliminary findings highlight the role of 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.