PSMC2 promotes the progression of gastric cancer via induction of RPS15A/mTOR pathway.

As one of the most common malignant tumors, it is particularly important to further understand the development mechanism of gastric cancer and to find more effective therapeutic target genes. The results of immunohistochemical staining showed that PSMC2 was upregulated in gastric cancer. Cell function experiments indicated that PSMC2 knockdown inhibited the proliferation, clone formation and migration of gastric cancer cells, and induced apoptosis. In vivo experiments further showed that PSMC2 knockdown suppressed tumor growth. RPS15A and mTOR pathway were identified the downstream gene and pathway of PSMC2 by GeneChip and IPA. PSMC2 knockdown inhibited RPS15A expression and mTOR pathway, which was neutralized by RPS15A overexpression. Overexpression of RPS15A promoted the proliferation and migration of gastric cancer cells, which alleviated the inhibitory effect caused by PSMC2 knockdown to a certain extent. The mTOR pathway inhibitor Torin1 partially restored the promoting role of RPS15A overexpression on the gastric cancer cell proliferation. Furthermore, bioinformatics analysis and dual-luciferase reporter assays showed that PSMC2 and RPS15A competitively bound to hsa-let-7c-3p. Inhibition of hsa-let-7c-3p promoted the migration of MGC-803 cells and reduced the apoptosis level, while simultaneous inhibition PSMC2 and hsa-let-7c-3p restored the migration and apoptosis levels of gastric cancer cells. In conclusion, PSMC2 and RPS15A were highly expressed in gastric cancer. PSMC2 enhanced RPS15A levels by targeting hsa-let-7c-3p, and then activated mTOR pathway, thereby promoting the progression of gastric cancer. © 2022. The Author(s).

Citation

Tao Liu, Junling Zhang, Hu Chen, Tashi Bianba, Yisheng Pan, Xin Wang, Yong Jiang, Zhen Yang. PSMC2 promotes the progression of gastric cancer via induction of RPS15A/mTOR pathway. Oncogenesis. 2022 Mar 07;11(1):12

PMID: 35256584

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