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

Abstract

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.

Enabling factor for cancer hallmark acquisition: Small nucleolar RNA host gene 17

“…The impairment of caretaker mechanisms, such as DNA repair defect, aberrant cell cycle regulation, and abnormal telomere DNA maintenance mechanisms, can lead to genome instability ( 95 ). As described in the sustaining proliferative signaling section, SNHG17 has been found to inhibit cell cycle protein-dependent kinase inhibitor (CKI) p15, 16, 57, and to increase ( 16 , 19 , 20 , 96 ) cell cycle protein-dependent kinase CDK4 and CDK6 expression ( 20 , 23 ) to involve in aberrant cell cycle regulation.…”

“…The tumor suppressor-like properties of CKI have been reported in recent years ( 17 ), and lncRNAs can promote cancer cell proliferation and migration by decreasing CKI expression ( 18 ). SNHG17 acts as a suppressor of multiple CKIs in tumors; in addition to p57, SNHG17 can also inhibit p15 and p16, and this CKI inhibitory property contributes to increasing cell proliferation capacity ( 19 , 20 ). Moreover, RNA sequencing predicts that SNHG17 can interact with the transcription factor krupple-like factor 6 (KLF6) ( 21 ).…”

“…p21 may also exist downstream of SNHG17 considering the regulatory relationship between KLF6 and p21 ( 22 ). Furthermore, SNHG17 can enhance the expression of CDK4 and CDK6, promoting cell cycle progression ( 20 , 23 ).…”

Erratum to long non-coding RNA SNHG17 promotes gastric cancer progression by inhibiting P15 and P16

“…In the April 2019 issue of Translational Cancer Research , the article “Long non-coding RNA SNHG17 promotes gastric cancer progression by inhibiting P15 and P16 ” edited by Gao et al ( 1 ), was published with some errors in Figure 2D due to picture misuse and the Figure 2D should be corrected as below:…”