Molecular mechanisms of LncRNA-CASC2 competitively binding miR-193a-5p regulating GSDMD scorch death pathway reversing Cisplatin resistance in non-small cell lung cancer
LUO Shicheng XIAO Dongping HUANG Xiuling ZUO Wei HU Xiangdong DENG Zhihui
Department of General Medicine, Nanchang First Hospital, Jiangxi Province, Nanchang 330006, China
Abstract：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 successfully 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 GSDMD 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.
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