title: Up-regulation of miR-455-5p by the TGF-β-SMAD signalling axis promotes the proliferation of oral squamous cancer cells by targeting UBE2B.
abstract: MicroRNAs (miRNAs) are involved in the tumourigenesis of various cancers by regulating their downstream targets. To identify the changes of miRNAs in oral squamous cell carcinoma (OSCC), we investigated the expression profiles of miRNAs in 40 pairs of OSCC specimens and their matched non-tumour epithelial tissues. Our data revealed higher miR-455-5p expression in the tumour tissues than in the normal tissues; the expression was also higher in oral cancer cell lines than in normal keratinocyte cell lines. MiR-455-5p knockdown reduced both the anchorage-independent growth and the proliferative ability of oral cancer cells, and these factors increased in miR-455-5p-overexpressing cells. Furthermore, by analysing the array data of patients with cancer and cell lines, we identified ubiquitin-conjugating enzyme E2B (UBE2B) as a target of miR-455-5p, and further validated this using 3'-untranslated region luciferase reporter assays and western blot analysis. We also demonstrated that UBE2B suppression rescued the impaired growth ability of miR-455-5p-knockdown cells. Furthermore, we observed that miR-455-5p expression was regulated, at least in part, by the transforming growth factor-β (TGF-β) pathway through the binding of SMAD3 to specific promoter regions. Notably, miR-455-5p expression was associated with the nodal status, stage, and overall survival in our patients, suggesting that miR-455-5p is a potential marker for predicting the prognosis of patients with oral cancer. In conclusion, we reveal that miR-455-5p expression is regulated by the TGF-β-dependent pathway, which subsequently leads to UBE2B down-regulation and contributes to oral cancer tumourigenesis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.|National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan, ROC.
authors.forename: Chao-Min
authors.initials: CM
authors.lastname: Cheng
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan, ROC.
authors.forename: Shine-Gwo
authors.initials: SG
authors.lastname: Shiah
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan, ROC.
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Otolaryngology, Head and Neck Collaborative Oncology Group, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Jenn-Ren
authors.initials: JR
authors.lastname: Hsiao
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.|National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan, ROC.|Division of Hematology/Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Jang-Yang
authors.initials: JY
authors.lastname: Chang
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins / Q000378:metabolism*; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C583404:MIRN455 microRNA, human; D035683:MicroRNAs; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C471546:UBE2B protein, human; D044763:Ubiquitin-Conjugating Enzymes
keywords: TGF-β; UBE2B; microRNA; oral cancer