长链非编码RNA LINC01133调控肺腺癌细胞顺铂敏感性的作用及机制研究OA

Objective To investigate the regulatory role of LINC01133 in cisplatin sensitivity of lung adenocarcinoma cells and its underlying molecular mechanisms.Methods The lung adenocarcinoma wild-type cell line A549 and its cispla-tin-resistant derivative A549/DDP were selected as research subjects.Lentiviral transfection technology was used to con-struct A549 cells with stable LINC01133 overexpression and A549/DDP cells with stable LINC01133 knockdown,with empty vector negative control groups established simultaneously.The CCK-8 assay was employed to detect cisplatin resis-tance and proliferative activity.Wound healing assay was used to evaluate migration ability,colony formation assay to as-sess clonogenic capacity,Transwell assay to evaluate invasive ability,and flow cytometry to analyze cell cycle distribution.Additionally,transmission electron microscopy was performed to observe cellular ultrastructure.Western blotting,enzyme-linked immunosorbent assay(ELISA),and lactate dehydrogenase(LDH)release assay were combined to comprehensively evaluate pyroptosis levels from three dimensions:protein expression,inflammatory cytokine release,and cell membrane in-tegrity.Results Compared with controls,LINC01133 overexpression significantly enhanced cisplatin resistance in A549 cells,promoted their proliferation,migration,colony formation,and invasion capabilities,and concurrently reduced the pro-portion of cells in S phase.Regarding pyroptosis-related indicators,cells in the LINC01133 overexpression group main-tained intact ultrastructure,showed downregulated expression of pyroptosis-associated proteins Cleaved Caspase-1 and GS-DMD-N,and exhibited significantly reduced levels of inflammatory cytokines IL-1β and IL-18 as well as decreased LDH release rate in the supernatant.Conversely,LINC01133 knockdown in A549/DDP cells significantly reversed cisplatin re-sistance and the aforementioned malignant phenotypes,accompanied by enhanced pyroptosis,with all related indicators showing opposite and significant changes.All differences were statistically significant(P<0.001 or P<0.000 1).Conclusion LINC01133 enhances cisplatin resistance and malignant biological phenotypes in lung adenocarcinoma cells by inhibiting Caspase-1/GSDMD signaling pathway-mediated pyroptosis,suggesting that LINC01133 may serve as a potential interven-tion target for reversing cisplatin resistance.