LncRNA-ATB Promotes Cisplatin Resistance in Lung Adenocarcinoma Cells by Targeting the miR-200a/?-Catenin Pathway.

ABSTRACT: Introduction:Lung adenocarcinoma (LUAD), which is associated with high morbidity and mortality, is prone to cisplatin resistance, resulting in poor patient prognosis. Long non-coding RNAs (lncRNAs) have complex biological functions in a variety of tumors. Elucidating the underlying molecular mechanisms between lncRNA and cisplatin resistance in LUAD is expected to enable identification of new targets for drug development. Methods:Cell proliferation was measured by CCK-8 assay and cell apoptosis was detected using flow cytometry analysis. Luciferase reporter assay was conducted to determine the interaction between lncRNA and MicroRNA. Gene expression was evaluated by Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction and Western blot analysis. Results:Long non-coding RNA activated by TGF-? (lncRNA-ATB) was shown to be significantly up-regulated in A549 cells resistant to cisplatin/cis-dichlorodiammineplatinum (II) (cis-DDP) (A549/CDDP cells), compared with corresponding levels in parental A549 cells. Overexpression of lncRNA-ATB significantly elevated cisplatin resistance in LUAD cell lines (A549 and H1975 cells), and this was associated with activation of apoptosis-related genes. Conversely, silencing of lncRNA-ATB decreased cisplatin resistance in LUAD cells. Mechanistically, lncRNA-ATB increased expression of ?-catenin by directly binding to MicroRNA-200a (miR-200a), thereby promoting cell survival and cisplatin resistance. Transfection with a miR-200a mimic or treatment with the ?-catenin downstream pathway inhibitor IWR-1 could reverse the phenotypes induced by lncRNA-ATB overexpression. Conclusion:In summary, this study revealed that lncRNA-ATB is dramatically up-regulated in cisplatin-resistant LUAD cell lines, and that lncRNA-ATB facilitates cell survival by targeting the miR-200a/?-catenin pathway in these cells.

SUBMITTER: Tang W 

PROVIDER: S-EPMC7090201 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature