中国病理生理杂志2025，Vol.41Issue(3)：433-443,11.DOI:10.3969/j.issn.1000-4718.2025.03.003
LINC00973通过hsa-miR-150-5p/ABCG5轴调控非小细胞肺癌多药耐药
LINC00973 regulates multidrug resistance of non-small-cell lung cancer through hsa-miR-150-5p/ABCG5 axis
摘要
Abstract
AIM:This study aims to investigate the mechanism by which LINC00973 regulates multidrug re-sistance of non-small-cell lung cancer(NSCLC).METHODS:The GEPIA database was employed to analyze the expres-sion levels of LINC00973 in NSCLC and its correlation with patient prognosis in clinical settings.RT-qPCR was utilized to assess LINC00973 expression in various NSCLC cell lines and chemoresistant cells.The migration,invasion,stemness ca-pacity,and drug sensitivity of NSCLC cells with either overexpression or knockdown of LINC00973 were evaluated using wound healing assay,Transwell assay,sphere formation assay,and CCK-8 assay.RNA sequencing was conducted on LINC00973-overexpressing and parental NSCLC cells to identify dysregulated pathways and targets.The LncBase Pre-dicted v.2 and TargetScan databases were used to predict the microRNAs(miRNAs)co-bound by LINC00973 and their target genes.Mimics and inhibitors of candidate miRNAs were synthesized and transfected into NSCLC cells subjected to LINC00973 overexpression or knockdown.Changes in the expression level of LINC00973,and the mRNA and protein ex-pression levels of its target genes were assessed using RT-qPCR and Western blot.RESULTS:Analysis of the GEPIA da-tabase revealed that LINC00973 was significantly up-regulated in lung adenocarcinoma and lung squamous cell carcino-ma,correlating with poor prognosis of NSCLC patients.The LINC00973 expression was elevated in various NSCLC and chemoresistant cell lines(A549/DDP and A549/5-FU).Overexpression of LINC00973 in A549 and H520 cells markedly enhanced their migration,invasion,and stemness capabilities,while concurrently reducing sensitivity to chemotherapy and targeted therapies.RNA sequencing,along with RT-qPCR results,indicated that ATP-binding cassette transporter G5(ABCG5)was activated in LINC00973-overexpressing A549 and H520 cells.Further database analyses and dual trans-fection experiments confirmed that LINC00973 regulated ABCG5 expression through competitive binding with hsa-miR-150-5p.CONCLUSION:LINC00973,which is aberrantly up-regulated in NSCLC specimens and associated with poor clinical prognosis,promotes the expression of ABCG5 through competitive binding with hsa-miR-150-5p.This interaction leads to en-hanced invasion,stemness,and multidrug resistance in NSCLC cells.关键词
非小细胞肺癌/多药耐药/LINC00973/微小RNA-150-5p/ATP结合盒转运蛋白G5Key words
non-small-cell lung cancer/multidrug resistance/LINC00973/microRNA-150-5p/ATP-binding cassette transporter G5分类
临床医学引用本文复制引用
夏云秀,董洪亮,刘翠兰,王飞,崔冰洁,陈微微,杜静..LINC00973通过hsa-miR-150-5p/ABCG5轴调控非小细胞肺癌多药耐药[J].中国病理生理杂志,2025,41(3):433-443,11.基金项目
国家自然科学基金资助项目(No.31900441 （）
No.82373097) （）
山东省自然科学基金资助项目(No.ZR2019MC026 （）
No.22QH192) （）
山东省中医药科技项目(No.Z20244106) （No.Z20244106）
