MALAT1/miR-101-3p/MCL1 axis mediates cisplatin resistance in lung cancer

Huaqi Wang; Li Wang; Guojun Zhang; Chunya Lu; Heying Chu; Rui Yang; Guoqiang Zhao

doi:10.18632/oncotarget.23483

MALAT1/miR-101-3p/MCL1 axis mediates cisplatin resistance in lung cancer

Oncotarget. 2017 Dec 14;9(7):7501-7512. doi: 10.18632/oncotarget.23483. eCollection 2018 Jan 26.

Authors

Huaqi Wang¹, Li Wang², Guojun Zhang¹, Chunya Lu¹, Heying Chu¹, Rui Yang¹, Guoqiang Zhao²

Affiliations

¹ Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
² School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, P.R. China.

Abstract

In this study, we investigated the mechanism by which lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) mediates cisplatin resistance in lung cancer. Lung cancer patients with high MALAT1 levels were associated with cisplatin resistance and low overall survival. Moreover, cisplatin-resistant A549/DDP cells showed higher MALAT1 expression than cisplatin-sensitive lung cancer cells (A549, H460, H1299 and SPC-A1). Dual luciferase reporter and RNA immunoprecipitation assays showed direct binding of miR-101-3p to MALAT1. MALAT1 knockdown in lung cancer cells resulted in miR-101-3p upregulation and increased cisplatin sensitivity. In addition, miR-101-3p decreased myeloid cell leukemia 1 (MCL1) expression by binding to the 3'-untranslated region (3'-UTR) of its mRNA. These results demonstrate that MALAT1/miR-101-3p/MCL1 signaling underlies cisplatin resistance in lung cancer.

Keywords: MALAT1; cisplatin; miR-101-3p; myeloid cell leukemia 1; resistance.