LncRNA-CASC2竞争性结合miR-193a-5p调控GSDMD焦亡通路逆转非小细胞肺癌顺铂耐药的分子机制

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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.

Key words： LncRNA-CASC2 miR-193a-5p GSDMD Drug resistance

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	LUO Shicheng XIAO Dongping HUANG Xiuling ZUO Wei HU Xiangdong DENG Zhihui

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LUO Shicheng XIAO Dongping HUANG Xiuling ZUO Wei HU Xiangdong DENG Zhihui. Molecular mechanisms of LncRNA-CASC2 competitively binding miR-193a-5p regulating GSDMD scorch death pathway reversing Cisplatin resistance in non-small cell lung cancer[J]. 中国当代医药, 2024, 31(1): 10-14.

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https://www.dangdaiyiyao.com/EN/ OR https://www.dangdaiyiyao.com/EN/Y2024/V31/I1/10

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