中国癌症防治杂志2025,Vol.17Issue(6):722-729,8.DOI:10.3969/j.issn.1674-5671.2025.06.10
miR-130a-3p靶向ATG2B调控顺铂耐药小细胞肺癌自噬
miR-130a-3p targets ATG2B to regulate autophagy in cisplatin-resistance small cell lung cancer
摘要
Abstract
Objective To investigate the role of miR-130a-3p in cisplatin-resistant small cell lung cancer(SCLC)and explore its underlying molecular mechanisms.Methods Cisplatin-resistant SCLC cell line(H446/EP)was established using a concentra-tion-gradient induction method.The SCLC cells were transfected with miR-130a-3p mimics via lipofection.Cell proliferation viability was assessed using the CCK-8 assay,while apoptosis rates and cell cycle distribution were analyzed by flow cytometry.Bioinformatics analysis was performed using TargetScan,TarBase,and miRWalk databases to predict the targeting relationship between miR-130a-3p and ATG2B.The expression levels of miR-130a-3p and ATG2B mRNA were detected by quantitative real-time PCR(qRT-PCR).Protein expression of autophagy-related proteins,including ATG2B,LC3B,p62,and Beclin1 were measured by Western blot.The fluorescence intensity of LC3B and p62 proteins was quantified by immunofluorescence to evaluate cellular autophagy activity.Results The resistance index of H446/EP cells was 6.465,with miR-130a-3p expression was significantly lower than in the sensitive parent cells.Restoring miR-130a-3p expression effectively inhibited proliferation and promoted apoptosis in the resistant cells(all P<0.05).Bioinformatics prediction indicated that ATG2B is a high-confidence target gene of miR-130a-3p.Overexpression of with miR-130a-3p suppressed the expression of the autophagy-related gene ATG2B,leading to decreased LC3B-Ⅱ/LC3B-Ⅰ ratio and Beclin1 levels(all P<0.05),while upregulating p62 levels(P<0.05).Conclusions miR-130a-3p mediates cisplatin resistance in SCLC cells through regulating ATG2B expression.Enhancing miR-130a expression may provide a novel strategy for overcoming platinum resis-tance in SCLC.关键词
小细胞肺癌/miR-130a/ATG2B/顺铂/耐药Key words
Small cell lung cancer/miR-130a-3p/ATG2B/Cisplatin/Resistance分类
医药卫生引用本文复制引用
米克日阿依·艾合买提,阿丽亚·奥斯曼,刘俊远,帕提古力·阿尔西丁..miR-130a-3p靶向ATG2B调控顺铂耐药小细胞肺癌自噬[J].中国癌症防治杂志,2025,17(6):722-729,8.基金项目
新疆维吾尔自治区自然科学基金面上项目(2022D01C294) (2022D01C294)
"天山英才"医药卫生高层次人才培养计划领军人才项目(TSYC202301A068) (TSYC202301A068)