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

Authors Tang W, Yu X, Zeng R, Chen L

Received 1 December 2019

Accepted for publication 2 March 2020

Published 18 March 2020 Volume 2020:12 Pages 2001—2014

DOI https://doi.org/10.2147/CMAR.S240695

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Seema Singh


Weiwei Tang, 1, 2,* Xiuyi Yu, 3,* Ru Zeng, 1, 2 Lilin Chen 1, 2

1Department of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research, Cancer Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian Province 361003, People’s Republic of China; 2Teaching Hospital of Fujian Medical University, Xiamen, Fujian Province 361003, People’s Republic of China; 3Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, Fujian Province 361003, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Lilin Chen
Department of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research, Cancer Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University; Teaching Hospital of Fujian Medical University, No. 55 Zhenhai Road, Xiamen, Fujian Province 361003, People’s Republic of China
Tel +86 0592 2137275
Fax +86 0592 2137279
Email chenlilin163@163.com

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-β (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 β-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 β-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/β-catenin pathway in these cells.

Keywords: lncRNA-ATB, miR-200a, β-catenin, lung adenocarcinoma, cisplatin resistance


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