Anticancer Drug-Induced Epithelial-Mesenchymal Transition via p53/miR-34a axis in A549/ABCA3 Cells

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Title Anticancer Drug-Induced Epithelial-Mesenchymal Transition via p53/miR-34a axis in A549/ABCA3 Cells
 
Creator Yamamoto, Ayano
Kawami, Masashi
Konaka, Takashi
Takenaka, Shinnosuke
Yumoto, Ryoko
Takano, Mikihisa
 
Description PURPOSE. Several anticancer drugs including bleomycin (BLM) and methotrexate (MTX) cause serious lung diseases such as pulmonary fibrosis. Although evidences showing the association of epithelial-mesenchymal transition (EMT) with pulmonary fibrosis are increasing, the mechanism underlying anticancer drug-induced EMT has been poorly understood. On the other hand, miR-34a, a non-coding small RNA, has been highlighted as a key factor to regulate EMT in lung. In this study, we elucidated the role of miR-34a in anticancer drug-induced EMT using A549/ABCA3 cells as a novel type II alveolar epithelium model. METHODS. Expression levels of α-smooth muscle actin (α-SMA) mRNA, miR-34a, and p53 were evaluated by real-time PCR and western blot analysis, respectively. RESULTS. BLM and MTX induced EMT-like morphological changes and increase in mRNA expression level of α-SMA, an EMT marker. Also, both drugs increased the expression level of miR-34a. Furthermore, mRNA expression level of α-SMA was enhanced by introduction of miR-34a mimic into A549/ABCA3 cells. To examine the mechanism underlying drug-induced enhancement of miR-34a expression, we focused on p53/miR-34a axis. Both drugs upregulated protein expression of p53, an inducer of miR-34a, as well as phosphorylation of Ser15 in p53. CONCLUSIONS. These findings indicated that p53/miR-34a axis may contribute to anticancer drug-induced EMT in type II alveolar epithelial cells.
 
Publisher Canadian Society for Pharmaceutical Sciences
 
Contributor Hidetoshi Tahara, Hiroshima University
Akira Shimamoto, Sanyo-Onoda City University
Toru Koike, Hiroshima University
Chieko Yamamoto for her assistance in the establishment of A549/ABCA3 cells
Japan Society for the Promotion of Science
 
Date 2019-10-10
 
Type info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
 
Format application/pdf
 
Identifier https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/30660
10.18433/jpps30660
 
Source Journal of Pharmacy & Pharmaceutical Sciences; ##issue.vol## 22 (2019): Pages 365 - 629; 516-524
Journal of Pharmacy & Pharmaceutical Sciences; Vol 22 (2019): Pages 365 - 629; 516-524
1482-1826
1482-1826
 
Language eng
 
Relation https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/30660/21535
 
Rights Copyright (c) 2019 Journal of Pharmacy & Pharmaceutical Sciences
http://creativecommons.org/licenses/by-sa/4.0
 

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