OASL knockdown inhibits the progression of stomach adenocarcinoma by regulating the mTORC1 signaling pathway.

Weizhu Zhao, Haiying Yang, Luguang Liu, Xianlin Qu, Jishuang Ding, Hang Yu, Botao Xu, Siwei Zhao, Guangmin Xi, Ligang Xing, Jie Chai

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2023 Mar

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The present study investigated the effects of 2'-5' oligoadenylate synthetase-like (OASL) on the biological functions of stomach adenocarcinoma (STAD) cells and tumor formation in nude mice. The differential expression levels of OASL in the different cancer types from TCGA dataset were analyzed using gene expression profiling interactive analysis. Overall survival and the receiver operating characteristic were analyzed using the KM plotter and R, respectively. Furthermore, OASL expression and its effects on the biological functions of STAD cells were detected. The possible upstream transcription factors of OASL were predicted using JASPAR. The downstream signaling pathways of OASL were analyzed using GSEA. Tumor formation experiments were performed to evaluate the effect of OASL on tumor formation in nude mice. The results showed that OASL was highly expressed in STAD tissues and cell lines. OASL knockdown markedly inhibited cell viability, proliferation, migration, and invasion and accelerated STAD cell apoptosis. Conversely, OASL overexpression had the opposite effect on STAD cells. JASPAR analysis revealed that STAT1 is an upstream transcription factor of OASL. Furthermore, GSEA showed that OASL activated the mTORC1 signaling pathway in STAD. The protein expression levels of p-mTOR and p-RPS6KB1 were suppressed by OASL knockdown and promoted by OASL overexpression. The mTOR inhibitor, rapamycin, markedly reversed the effect of OASL overexpression on STAD cells. Additionally, OASL promoted tumor formation and increased tumor weight and volume in vivo. In conclusion, OASL knockdown suppressed the proliferation, migration, invasion, and tumor formation of STAD cells by inhibiting the mTOR signaling pathway. © 2023 Federation of American Societies for Experimental Biology.

Citation

Weizhu Zhao, Haiying Yang, Luguang Liu, Xianlin Qu, Jishuang Ding, Hang Yu, Botao Xu, Siwei Zhao, Guangmin Xi, Ligang Xing, Jie Chai. OASL knockdown inhibits the progression of stomach adenocarcinoma by regulating the mTORC1 signaling pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2023 Mar;37(3):e22824