title: miR-31 targets ARID1A and enhances the oncogenicity and stemness of head and neck squamous cell carcinoma.
abstract: miR-31 is oncogenic for head and neck squamous cell carcinoma (HNSCC). Proteins containing the AT-rich interacting domain (ARID) modulate the accessibility of chromatin to the transcription machinery needed for gene expression. In this study, we showed that miR-31 was able to target ARID1A in HNSCC. HNSCC tumors had an inverse miR-31 and ARID1A expression. miR-31 associated oncogenicities were rescued by ARID1A expression in HNSCC cells. Furthermore, ARID1A repressed the stemness properties and transcriptional activity of Nanog/OCT4/Sox2/EpCAM via the protein's affinity for AT-rich sites within promoters. HNSCC patients with tumors having high level of miR-31 expression and high levels of Nanog/OCT4/Sox2/EpCAM expression, together with low level of ARID1A expression, were found to have the worst survival. This study provides novel mechanistic clues demonstrating that miR-31 inhibits ARID1A and that this enriches the oncogenicity and stemness of HNSCC.
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Lu
authors.affiliation: Department of Dentistry, National Yang-Ming University, Taipei, Taiwan.|Department of Dentistry, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Chung-Ji
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Department of Dentistry, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsi-Feng
authors.initials: HF
authors.lastname: Tu
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yu-Tung
authors.initials: YT
authors.lastname: Chung
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.|Department of Dentistry, National Yang-Ming University, Taipei, Taiwan.|Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Cheng-Chieh
authors.initials: CC
authors.lastname: Yang
authors.affiliation: Department of Dentistry, National Yang-Ming University, Taipei, Taiwan.|Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shou-Yen
authors.initials: SY
authors.lastname: Kao
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.|Department of Dentistry, National Yang-Ming University, Taipei, Taiwan.|Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Kuo-Wei
authors.initials: KW
authors.lastname: Chang
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.|Department of Dentistry, National Yang-Ming University, Taipei, Taiwan.|Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Lin
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D000071858:Epithelial Cell Adhesion Molecule / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000166:cytology; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D055748:SOXB1 Transcription Factors / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; C112476:ARID1A protein, human; D004268:DNA-Binding Proteins; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors
keywords: ARID1A; cancer; miR-31; stem cell; suppressor