title: The tumor-suppressive microRNA-23b/27b cluster regulates the MET oncogene in oral squamous cell carcinoma.
abstract: Our recent studies of microRNA (miRNA) expression signatures in human cancers revealed that two clustered miRNAs, microRNA-23b (miR-23b) and microRNA-27b (miR‑27b), were significantly reduced in cancer tissues. Few reports have provided functional analyses of these clustered miRNAs in oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the functional significance of miR-23b and miR-27b in OSCC and to identify novel miR-23b/27b-mediated cancer pathways and target genes involved in OSCC oncogenesis and metastasis. Expression levels of miR-23b and miR-27b were significantly reduced in OSCC specimens. Restoration of miR-23b or miR-27b in cancer cells revealed that both miRNAs significantly inhibited cancer cell migration and invasion. Our in silico analyses and luciferase reporter assays showed that the receptor tyrosine kinase MET, was directly regulated by these miRNAs. Moreover, downregulating the MET gene by use of siRNA significantly inhibited cell migration and invasion by OSCC cells. The identification of novel molecular pathways regulated by miR-23b and miR-27b may lead to a better understanding of the oncogenesis and metastasis of this disease.
authors: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan.
authors: Ichiro
authors: I
authors: Fukumoto
authors: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan.
authors: Keiichi
authors: K
authors: Koshizuka
authors: Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan.
authors: Toyoyuki
authors: T
authors: Hanazawa
authors: Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan.
authors: Naoko
authors: N
authors: Kikkawa
authors: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima-shi, Kagoshima 890-8520, Japan.
authors: Ryosuke
authors: R
authors: Matsushita
authors: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan.
authors: Akira
authors: A
authors: Kurozumi
authors: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan.
authors: Mayuko
authors: M
authors: Kato
authors: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan.
authors: Atsushi
authors: A
authors: Okato
authors: Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan.
authors: Yoshitaka
authors: Y
authors: Okamoto
authors: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan.
authors: Naohiko
authors: N
authors: Seki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D009362:Neoplasm Metastasis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism*
chemical_list: C552430:MIRN23a microRNA, human; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met