Research Papers:
Transcriptional suppression of microRNA-27a contributes to laryngeal cancer differentiation via GSK-3β-involved Wnt/β-catenin pathway
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Abstract
Sheng Chen1, Yuan-Yuan Sun1, Zhao-Xiong Zhang1, Yun-Hui Li2, Zhen-Ming Xu3, Wei-Neng Fu1
1Department of Medical Genetics, China Medical University, Shenyang, 110122, P.R. China
2Department of Laboratory Medicine, No. 202 Hospital of PLA, Shenyang, 110003, P.R. China
3Department of Otolaryngology, No. 463 Hospital of PLA, Shenyang, 110007, P.R. China
Correspondence to:
Yun-Hui Li, email: [email protected]
Zhen-Ming Xu, email: [email protected]
Wei-Neng Fu, email: [email protected]
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.
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PII: 14769