Mechanism of GRIM-19 regulating signal transducer and activators of transcription 3 signaling pathway to inhibit the growth and proliferation of renal cell carcinoma
Objective To study the specific mechanism of GRIM-19 inhibiting the growth and pro-liferation of renal cell carcinoma(RCC).Methods The patients with renal cell carcinoma by nephrecto-my in this urology department were selected from September 2021 to September 2022,and tumor tissues were obtained from patients with RCC(30 cases,7 patients with stage 1,8 patients with stage 2,8 patients with stage 3,and 7 patients with stage 4),and adjacent normal tissues were obtained from controls(10 cases).After overexpression of GRIM-19 in RCC cells,the expression levels of signal transducer and activators of transcription 3(STAT3)and its downstream pathway proteins were detected by RT-qPCR and Western blotting,and the proliferation level of RCC cells was determined by methyl thiazolyl tetrazolium(MTT)assay,the level of apoptosis was measured by flow cytometry.SPSS 20.0 was used for analysis.One-way ANOVA was used for sample mean comparison,and T-test was used for pairwise comparison.Results GRIM-19 was down-expressed in RCC cells as compared with normal tissues,while SATA3 and its downstream proteins were highly expressed.The expression levels of GRIM-19(4.45±1.01),B cell lymphoma/leukemia-2 associated X protein(bax)(2.11±0.30)and cysteinyl aspartate-specific protease(Caspase)-9(1.87±0.09)were significantly increased in the adenovirus infection cells overexpressing GRIM-19 as compared with those in the 786-0 cells infected with empty adenovirus(1.62±0.07,1.47±0.08 and 1.23±0.50 respectively).The expression levels of STAT3,B cell lymphoma/leukemia-XL(bcl-XL)and Cyclin B1 in the adenovirus infection cells overexpressing GRIM-19 were significantly lower than those in the control group(1.68±0.70 vs.1.08±0.20;0.91±0.30 vs.0.67±0.40;1.38±0.20 vs.0.93±0.09).In addition,interferon(IFN)-β and ATRA could inhibit the growth and induce apopto-sis of RCC cells.As compared with those of IFN-β-GRIM-19 group(15.30±2.60)and ATRA-GRIM-19 group(14.60±2.80),the apoptosis of 786-O cells in IFN-B-ATRA-GRIM-19 group(21.70±3.10)increased significantly.Conclusion GRIM-19 expression in RCC is closely associated with SATA3-induced gene overexpression,and GRIM-19 inhibits growth and proliferation of RCC cells by regulating STAT3 signa-ling pathway.
Renal cell carcinomaGRIM-19Signal transducer and activators of transcription 3ProliferationApoptosis
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