標題: Periostin promotes epithelial-mesenchymal transition via the MAPK/miR-381 axis in lung cancer
作者: Hu, Wei-Wei
Chen, Po-Chun
Chen, Jun-Ming
Wu, Yue-Ming
Liu, Po-Yi
Lu, Chih-Hao
Lin, Yu-Feng
Tang, Chih-Hsin
Chao, Chia-Chia
生物資訊及系統生物研究所
Institude of Bioinformatics and Systems Biology
關鍵字: periostin;lung cancer;epithelial-mesenchymal transition;miR-381;MAPK
公開日期: 5-Sep-2017
摘要: 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.
URI: http://dx.doi.org/10.18632/oncotarget.19273
http://hdl.handle.net/11536/146019
ISSN: 1949-2553
DOI: 10.18632/oncotarget.19273
期刊: ONCOTARGET
Volume: 8
起始頁: 62248
結束頁: 62260
Appears in Collections:Articles