Molecular mechanisms of LncRNA-CASC2 competitively binding miR-193a-5p regulating GSDMD scorch death pathway reversing Cisplatin re-sistance in non-small cell lung cancer
Objective To explore the molecular mechanism of the competitive binding of LncRNA-CASC2 to miR-193a-5p in regulating GSDMD focal death pathway to reverse cisplatin resistance in non-small cell lung cancer.Methods Non-small cell lung cancer(NSCLC)cell line A549 was selected to establish a drug-resistant strain A549/DDP,and the sensitivity of the cell to cisplatin was detected by CCK8 to verify whether the drug-resistant cell line was success-fully established.The expression of CASC2 in A549 and A549/DDP cells and its effect on the expression of GSDMD2 and miR-193a-5p were detected by PCR.The binding sites of LncRNA-CASC2 and miR-193a-5p,miR-193a-5p and GSD-MD were predicted by bioinformatics software.The target relationship between CASC2 and miR-193a-5p and miR-193a-5p and GSDMD was analyzed by luciferase reporter gene,and the competitive binding of LncRNA-CASC2 to miR-193a-5p was detected by Western blot.Results The semi-inhibitory concentration of A549/DDP cells was more than 10 times that of A549 cells,indicating that the drug-resistant cell line A549/DDP had been successfully constructed.The expression level of CASC2 in A549/DDP was lower than that in A549(P＜0.05).CASC2 mimics inhibited the expression of miR-193a-5p in cells,while GSDMD expression was up-regulated(P＜0.05).There was a significant targeting relationship between CASC2 and miR-193a-5p,and between miR-193a-5p and GSDMD(P＜0.05).Conclusion The low expression of LncRNA-CASC2 and miR-193a-5p in NSCLC cells and the high expression of GSDMD are closely related to the chemotherapy resistance of NSCLC.The interaction of LncRNA-CASC2 and miR-193a-5p regulates GSDMD and promotes the drug resistance of tumor cells.
国家科技期刊平台
NSTL
维普
万方数据
