Objective:To investigate the effect of TRPM8 on the proliferation and apoptosis of renal cancer cells through the JNK signaling pathway through the regulation of autophagy. Methods:qRT-PCR was used to detect the expression of TRPM8 in renal cancer cells (A498, GRC-1, 786-0); Transfection of A498 cells with shRNA to construct stable cell lines with low expression of TRPM8; qRT-PCR and Western blotting was used to verify the interference efficiency of shRNA; Cell colony formation assay was used to detect A498 cell proliferation after silencing TRPM8; Cell flow cytometry was used to detect the apoptotic capacity of A498 cells after silencing TRPM8; Autophagy detection kit was used to detect changes in autophagy flux of A498 cells after silencing TRPM8; Western blotting was used to detect changes in autophagy-related markers (ATG3, ATG5, ATG6, ATG7, and ATG12) and expression of JNK pathway-related proteins after silencing TRPM8. Results:TRPM8 was highly expressed in renal cancer cells, and TRPM8 expression was significantly reduced after transfection of TRPM8 shRNA (P<0.01); After TRPM8 was silenced, the proliferation ability of A498 cells decreased significantly (P<0.01), and the apoptosis rate increased significantly (P<0.01); Transfection of TRPM8 shRNA and A498 cells also significantly reduced autophagy flux (P<0.05), and ATG3, ATG5, ATG6, ATG7 and ATG12 protein expressions also decreased (all P<0.05); After TRPM8 silencing, the level of phosphorylation of JNK decreased (P<0.05). After using JNK inhibitor (SP600125), the levels of ATG5 and ATG7 protein decreased significantly (both P<0.05). Conclusion:Silent TRPM8 channel-mediated autophagy regulation inhibits the proliferation of renal cancer cells through the JNK signaling pathway and promotes their apoptosis.
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