title: Potential of tumor-suppressive miR-596 targeting LGALS3BP as a therapeutic agent in oral cancer.
abstract: The incidence and mortality statistics for oral squamous cell carcinoma (OSCC) were 10th and 12th, respectively, in human cancers diagnosed worldwide in 2008. In this study, to identify novel tumor-suppressive microRNAs (TS-miRNAs) and their direct targets in OSCC, we performed methylation-based screening for 43 miRNAs encoded by 46 miRNA genes located within 500 bp downstream of 40 CpG islands and genome-wide gene expression profiling in combination with a prediction database analysis, respectively, in 18 cell lines, resulting in the identification of a novel TS-miRNA miR-596 directly targeting LGALS3BP/Mac-2 BP/90K. DNA hypermethylation of CpG island located 5'-upstream of miR-596 gene was frequently observed in OSCC cell lines (100% of 18 cell lines) and primary OSCC cases (46.2 and 76.3% of 26 Japanese and 38 Thais primary cases, respectively) in a tumor-specific manner. The ectopic transfection of double-stranded RNA (dsRNA) mimicking miR-596 or specific small interfering RNA for LGALS3BP significantly induced growth inhibition and apoptosis in cell lines lacking miR-596 expression or overexpressing LGALS3BP, respectively, in a manner associated with a suppression of ERK1/2 phosphorylation. Moreover, we also mention the effect of dsRNA mimicking miR-596 on the growth of an OSCC cell line in vivo. Our findings define a central role for miR-596 in OSCC and suggest the potential of miR-596 as an anticancer agent for miRNA replacement therapy in OSCC.
authors.affiliation: Department of Molecular Cytogenetics, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Endo
authors.forename: Tomoki
authors.initials: T
authors.lastname: Muramatsu
authors.forename: Mayuko
authors.initials: M
authors.lastname: Furuta
authors.forename: Narikazu
authors.initials: N
authors.lastname: Uzawa
authors.forename: Atiphan
authors.initials: A
authors.lastname: Pimkhaokham
authors.forename: Teruo
authors.initials: T
authors.lastname: Amagasa
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kozaki
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays; D016326:Extracellular Matrix Proteins
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D006023:Glycoproteins; D035683:MicroRNAs; D012330:RNA, Double-Stranded; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins; C579843:MIRN596 microRNA, human