title: Tumor suppressive microRNA-133a regulates novel targets: moesin contributes to cancer cell proliferation and invasion in head and neck squamous cell carcinoma.
abstract: Recently, many studies suggest that microRNAs (miRNAs) contribute to the development, invasion and metastasis of various types of human cancers. Our recent study revealed that expression of microRNA-133a (miR-133a) was significantly reduced in head and neck squamous cell carcinoma (HNSCC) and that restoration of miR-133a inhibited cell proliferation, migration and invasion in HNSCC cell lines, suggesting that miR-133a function as a tumor suppressor. Genome-wide gene expression analysis of miR-133a transfectants and TargetScan database showed that moesin (MSN) was a promising candidate of miR-133a target gene. MSN is a member of the ERM (ezrin, radixin and moesin) protein family and ERM function as cross-linkers between plasma membrane and actin-based cytoskeleton. The functions of MSN in cancers are controversial in previous reports. In this study, we focused on MSN and investigated whether MSN was regulated by tumor suppressive miR-133a and contributed to HNSCC oncogenesis. Restoration of miR-133a in HNSCC cell lines (FaDu, HSC3, IMC-3 and SAS) suppressed the MSN expression both in mRNA and protein level. Silencing study of MSN in HNSCC cell lines demonstrated significant inhibitions of cell proliferation, migration and invasion activities in si-MSN transfectants. In clinical specimen with HNSCC, the expression level of MSN was significantly up-regulated in cancer tissues compared to adjacent non-cancerous tissues. These data suggest that MSN may function as oncogene and is regulated by tumor suppressive miR-133a. Our analysis data of novel tumor-suppressive miR-133a-mediated cancer pathways could provide new insights into the potential mechanisms of HNSCC oncogenesis.
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Nijiro
authors.initials: N
authors.lastname: Nohata
authors.forename: Miki
authors.initials: M
authors.lastname: Fuse
authors.forename: Toyoyuki
authors.initials: T
authors.lastname: Hanazawa
authors.forename: Naoko
authors.initials: N
authors.lastname: Kikkawa
authors.forename: Lisa
authors.initials: L
authors.lastname: Fujimura
authors.forename: Haruko
authors.initials: H
authors.lastname: Watanabe-Takano
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Yamada
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yoshino
authors.forename: Hideki
authors.initials: H
authors.lastname: Enokida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; C071058:moesin