title: Transcriptional suppression of microRNA-27a contributes to laryngeal cancer differentiation via GSK-3β-involved Wnt/β-catenin pathway.
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.
authors.affiliation: Department of Medical Genetics, China Medical University, Shenyang, 110122, P.R. China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Medical Genetics, China Medical University, Shenyang, 110122, P.R. China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Sun
authors.affiliation: Department of Medical Genetics, China Medical University, Shenyang, 110122, P.R. China.
authors.forename: Zhao-Xiong
authors.initials: ZX
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, No. 202 Hospital of PLA, Shenyang, 110003, P.R. China.
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, No. 463 Hospital of PLA, Shenyang, 110007, P.R. China.
authors.forename: Zhen-Ming
authors.initials: ZM
authors.lastname: Xu
authors.affiliation: Department of Medical Genetics, China Medical University, Shenyang, 110122, P.R. China.
authors.forename: Wei-Neng
authors.initials: WN
authors.lastname: Fu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C000607071:RARA protein, human; D000072482:Retinoic Acid Receptor alpha; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D051176:beta Catenin; D014212:Tretinoin; D000071679:Glycogen Synthase Kinase 3 beta
keywords: ATRA; GSK-3β; differentiation; laryngeal cancer; miR-27a