LINC00973 regulates multidrug resistance of non-small-cell lung cancer through hsa-miR-150-5p/ABCG5 axis
10.3969/j.issn.1000-4718.2025.03.003
- VernacularTitle:LINC00973通过hsa-miR-150-5p/ABCG5轴调控非小细胞肺癌多药耐药
- Author:
Yunxiu XIA
1
;
Hongliang DONG
;
Cuilan LIU
;
Fei WANG
;
Bingjie CUI
;
Weiwei CHEN
;
Jing DU
Author Information
1. 滨州医学院附属医院医学研究中心,山东 滨州 256600;滨州医学院附属医院妇科,山东 滨州 256600
- Publication Type:Journal Article
- Keywords:
non-small-cell lung cancer;
multidrug resistance;
LINC00973;
microRNA-150-5p;
ATP-binding cassette transporter G5
- From:
Chinese Journal of Pathophysiology
2025;41(3):433-443
- CountryChina
- Language:Chinese
-
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.
