Transcriptional suppression of microRNA-27a contributes to laryngeal cancer differentiation via GSK-3β-involved Wnt/β-catenin pathway.

// Sheng Chen 1 , Yuan-Yuan Sun 1 , Zhao-Xiong Zhang 1 , Yun-Hui Li 2 , Zhen-Ming Xu 3 , Wei-Neng Fu 1 1 Department of Medical Genetics, China Medical University, Shenyang, 110122, P.R. China 2 Department of Laboratory Medicine, No. 202 Hospital of PLA, Shenyang, 110003, P.R. China 3 Department of Otolaryngology, No. 463 Hospital of PLA, Shenyang, 110007, P.R. China Correspondence to: Yun-Hui Li, email: 18909882737@163.com Zhen-Ming Xu, email: zs840817@163.com Wei-Neng Fu, email: wnfu@cmu.edu.cn Keywords: laryngeal cancer, miR-27a, ATRA, differentiation, GSK-3β Received: November 04, 2016      Accepted: January 11, 2017      Published: January 20, 2017 ABSTRACT miR-27a regulates cell differentiation in a variety of diseases. However, whether and how miR-27a participates in laryngeal cancer cell differentiation remains unknown. Therefore, we explored role and molecular mechanism of miR-27a in laryngeal cancer differentiation in the study. We found that miR-27a expression was inversely correlated with laryngeal cancer differentiation degree based on the clinical pathological diagnosis of each patient. miR-27 asignificantly rescued differentiation and inhibited β-catenin, LEF1, OCT4 and SOX2 in Wnt/β-catenin pathway in all-trans-retinoic acid (ATRA)-induced laryngeal cancer cells. Bindings of RARα to miR-27a and miR-27a to GSK-3β were confirmed by ChIP and Luciferase reporter assays, respectively. In conclusion, miR-27a is a negative regulator in laryngeal cancer differentiation. RARα-mediated miR-27a transcriptional inactivation releases the inhibition of miR-27a on GSK-3β leading to laryngeal cancer differentiation through GSK-3β-involved Wnt/β-catenin pathway, suggesting that miR-27a is a usefully therapeutic target at least in ATRA-induced laryngeal cancer differentiation.