TFAP2C-Activated MALAT1 Modulates the Chemoresistance of Docetaxel-Resistant Lung Adenocarcinoma Cells

Jing Chen; Xiaobei Liu; Yichen Xu; Kai Zhang; Jiayuan Huang; Banzhou Pan; Dongqin Chen; Shiyun Cui; Haizhu Song; Rui Wang; Xiaoyuan Chu; Xiaoli Zhu; Longbang Chen

doi:10.1016/j.omtn.2019.01.005

Molecular Therapy: Nucleic Acids (Mar 2019)

TFAP2C-Activated MALAT1 Modulates the Chemoresistance of Docetaxel-Resistant Lung Adenocarcinoma Cells

Jing Chen,
Xiaobei Liu,
Yichen Xu,
Kai Zhang,
Jiayuan Huang,
Banzhou Pan,
Dongqin Chen,
Shiyun Cui,
Haizhu Song,
Rui Wang,
Xiaoyuan Chu,
Xiaoli Zhu,
Longbang Chen

Affiliations

Jing Chen: Department of Respiratory, Zhongda Hospital, Southeast University, Nanjing, China; Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China
Xiaobei Liu: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China
Yichen Xu: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China
Kai Zhang: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China
Jiayuan Huang: Department of Medical Oncology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Jiangsu Institute of Cancer Research, Jiangsu, China
Banzhou Pan: Department of Medical Oncology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Jiangsu Institute of Cancer Research, Jiangsu, China
Dongqin Chen: Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Shiyun Cui: Department of Medical Oncology, The First Affiliated Hospital of Nanjing Medical University, Suzhou, Jiangsu, China
Haizhu Song: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China
Rui Wang: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China
Xiaoyuan Chu: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China
Xiaoli Zhu: Department of Respiratory, Zhongda Hospital, Southeast University, Nanjing, China; Corresponding author: Xiaoli Zhu, Department of Respiratory, Zhongda Hospital, Southeast University, Nanjing, China.
Longbang Chen: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China; Corresponding author: Longbang Chen, Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China.

DOI: https://doi.org/10.1016/j.omtn.2019.01.005
Journal volume & issue: Vol. 14
pp. 567 – 582

Abstract

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Chemoresistance remains a great obstacle in effective lung adenocarcinoma (LUAD) treatment. Previously, we verified the role of microRNA-200b (miR-200b) in the formation of docetaxel (DTX)-resistant LUAD cells. This study aims to investigate the mechanism underlying the low level of miR-200b in DTX-resistant LUAD cells. The real-time reverse transcription (RT2) lncRNA PCR array system was applied to explore lncRNAs that potentially regulated miR-200b in DTX-resistant LUAD cells. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) contributed to the low miR-200b level in DTX-resistant LUAD cells. Functional assays were conducted to determine the role of MALAT1 in regulating the growth and metastasis of parental and DTX-resistant LUAD cells. Investigation revealed the mechanism of the competing endogenous RNA (ceRNA) pathway. MALAT1 regulated miR-200b by acting as a ceRNA. MALAT1 modulated the sensitivity of LUAD cells to DTX. E2F transcription factor 3 (E2F3) and zinc-finger E-box binding homeobox 1 (ZEB1) were two targets of miR-200b and mediated the function of MALAT1 in DTX-resistant LUAD cells. Transcription factor AP-2 gamma (TFAP2C) and ZEB1 activated the MALAT1 transcription. In conclusion, TFAP2C-activated MALAT1 modulated the chemoresistance of LUAD cells by sponging miR-200b to upregulate E2F3 and ZEB1. Our findings may provide novel therapeutic targets and perspectives for LUAD treatment. Keywords: MALAT1, miR-200b, LUAD, chemoresistance

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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