title: Up-regulation of miR-187 modulates the advances of oral carcinoma by targeting BARX2 tumor suppressor.
abstract: Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. Aberrations in miRNA regulation are known to play important roles in OSCC pathogenesis. miR-187 was shown to be up-regulated in head and neck malignancies in our previous screening. This study further investigated the oncogenic potential, clinical implications, and targets of miR-187 in OSCC. We observed that miR-187 increased oncogenicity, particularly migration, of OSCC cells. miR-187 expression increased the xenografic tumorigenicity and metastasis in mice. In addition, metastatic human OSCC had higher miR-187 expression than did non-metastatic tumors. Through vigorous screening, we confirmed BarH-like Homeobox 2 (BARX2) gene as an miR-187 target. BARX2 expression suppressed the migration, invasion, anchorage-independent colony formation, and orthotopic tumorigenesis of OSCC cells. The migratory phenotype and neck metastasis induced by miR-187 was rescued by BARX2 expression. BARX2 expression was down-regulated in the vast majority of OSCC, and this down-regulation was particularly conspicuous in tumors with advanced nodal metastasis. In addition, plasma miR-187 was significantly higher in OSCC patients than in normal individuals. This study highlights the roles of miR-187-BARX2 in driving the carcinogenesis of OSCC. The results suggest that miR-187 is a potential serological marker for OSCC and that targeting of miR-187 might prove effective in attenuating nodal metastasis.
authors.affiliation: Institute of Oral Biology, 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
authors.affiliation: Institute of Oral Biology, 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.
authors.forename: Jennifer Chen-Yu
authors.initials: JC
authors.lastname: Chang
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ying-Chieh
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
authors.forename: En-Hao
authors.initials: EH
authors.lastname: Yu
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ssu-Hsueh
authors.initials: SH
authors.lastname: Tseng
authors.affiliation: Department of Dentistry, School 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: Institute of Oral Biology, 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
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D016147:Genes, Tumor Suppressor; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000097:blood / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D009333:Neck; D009857:Oncogenes; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014059:Tongue / Q000473:pathology; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: C491320:BARX2 protein, human; D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C571843:MIRN187 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering
keywords: BARX2; carcinoma; invasion; metastasis; miR-187