肿瘤药学2026，Vol.16Issue(3)：310-319,10.DOI:10.3969/j.issn.2095-1264.2026.03.07
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
The role and mechanism of long non-coding RNA LINC01133 in regulating cisplatin sensitivity in lung adenocarcinoma cells
摘要
Abstract
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.关键词
肺腺癌/LINC01133/顺铂耐药/细胞焦亡/Caspase-1/GSDMD通路Key words
Lung adenocarcinoma/LINC01133/Cisplatin resistance/Pyroptosis/Caspase-1/GSDMD pathway分类
医药卫生引用本文复制引用
徐绯翼,张璨,张有为,陈永刚..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[J].肿瘤药学,2026,16(3):310-319,10.基金项目
国家自然科学基金面上项目(81973346)、江苏省十四五医学重点学科(ZDXK202237). （81973346）
