Oncotarget

Research Papers:

Periostin promotes epithelial-mesenchymal transition via the MAPK/miR-381 axis in lung cancer

Wei-Wei Hu, Po-Chun Chen, Jun-Ming Chen, Yue-Ming Wu, Po-Yi Liu, Chih-Hao Lu, Yu-Feng Lin, Chih-Hsin Tang and Chia-Chia Chao _

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Oncotarget. 2017; 8:62248-62260. https://doi.org/10.18632/oncotarget.19273

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Abstract

Wei-Wei Hu1,*, Po-Chun Chen2,3,4,*, Jun-Ming Chen2, Yue-Ming Wu1, Po-Yi Liu5,6, Chih-Hao Lu2, Yu-Feng Lin7, Chih-Hsin Tang4,5,8 and Chia-Chia Chao9

1Department of Thoracic Surgery, Dongyang People's Hospital, Dongyang, China

2Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan

3Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan

4Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan

5Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan

6Department of Thoracic Surgery, Changhua Christian Hospital, Changhua, Taiwan

7Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan

8Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan

9Department of Respiratory Therapy, Fu-Jen Catholic University, New Taipei, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Chia-Chia Chao, email: 095457@mail.fju.edu.tw

Chih-Hsin Tang, email: chtang@mail.cmu.edu.tw

Keywords: periostin, lung cancer, epithelial-mesenchymal transition, miR-381, MAPK

Received: April 14, 2017    Accepted: May 29, 2017    Published: July 15, 2017

ABSTRACT

Periostin (POSTN, PN, or osteoblast-specific factor OSF-2) is a multifunctional cytokine that signals between the cell and the extracellular matrix. Periostin plays an important role in tumor development and is involved in carcinoma cell epithelial-mesenchymal transition (EMT), whereby mature epithelial cells undergo phenotypic morphological changes and become invasive, motile cells. Here, we discuss the molecular mechanisms involved in periostin-induced promotion of EMT in lung cancer cells. Online TCGA datasets demonstrate the prognostic relevance of periostin in lung cancer; a higher periostin level correlates with poor overall survival. Similarly, our IHC results show that high periostin expression is positively correlated with the EMT markers Snail and Twist, as well as stage of lung cancer. We found that recombinant periostin induces the EMT phenotype in lung cancer cells through the p38/ERK pathway, while pretreatment with chemical inhibitors prevented periostin-induced EMT induction. Moreover, we found that periostin regulates EMT by repressing microRNA-381 (miR-381) expression, which targets both Snail and Twist. Using the miR-381 mimic, we dramatically reversed periostin-induced Snail and Twist expression. Furthermore, periostin knockdown dramatically affected EMT markers and cell migration potential. The role of periostin in lung cancer progression is elucidated by the in vivo mouse model. Our findings indicate that changes in periostin expression in lung cancer may serve as a therapeutic target for the treatment of lung cancer metastasis.


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