title: Actin-related protein 2/3 complex subunit 5 (ARPC5) contributes to cell             migration and invasion and is directly regulated by tumor-suppressive microRNA-133a             in head and neck squamous cell carcinoma.
abstract: Our expression signatures of human cancers including head and neck squamous cell carcinoma (HNSCC) demonstrated that downregulation of microRNA-133a (miR-133a) were frequently observed in cancer cells. The restoration of miR-133a in cancer cells revealed that it functions as a tumor suppressor. In this study, we investigated the novel molecular targets of miR-133a in HNSCC cancer cells and its oncogenic function, especially as it contributes to cancer cell migration and invasion. The genome-wide gene expression analysis and bioinformatics study showed that actin-related protein 2/3 complex subunit 5 (ARPC5) is a candidate target of miR-133a. Furthermore, luciferase reporter assay demonstrated that ARPC5 is directly regulated by miR-133a. Silencing of ARPC5 revealed significant inhibition of cell migration and invasion in HNSCC cell lines, SAS, HSC3 and IMC-3. In HSC3 cells, restoration of miR-133a or silencing ARPC5 led to a reorganization of the actin cytoskeleton and a subsequent change in cell morphology to a round, bleb-like shape. The expression levels of ARPC5 were significantly higher in HNSCC tissues than in non-cancer tissues. Immunohistochemistry showed that the levels of ARPC5 expression were significantly higher in invasive cancer cells. ARPC5 contributed to cancer cell migration and invasion in HNSCC and this gene was directly regulated by miR-133a. Our analysis of novel tumor-suppressive miR‑133a-mediated cancer pathways provides new insights into the potential mechanisms of HNSCC oncogenesis.
authors.affiliation: Department of Functional Genomics, Chiba University Graduate                     School of Medicine, Chiba 260-8670, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Nijiro
authors.initials: N
authors.lastname: Nohata
authors.forename: Haruko
authors.initials: H
authors.lastname: Watanabe-Takano
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yoshino
authors.forename: Hideo
authors.initials: H
authors.lastname: Hidaka
authors.forename: Lisa
authors.initials: L
authors.lastname: Fujimura
authors.forename: Miki
authors.initials: M
authors.lastname: Fuse
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Hideki
authors.initials: H
authors.lastname: Enokida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Toyoyuki
authors.initials: T
authors.lastname: Hanazawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
mesh_terms: D020413:3' Untranslated Regions; D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001665:Binding Sites; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D034622:RNA Interference
chemical_list: D020413:3' Untranslated Regions; C573916:ARPC5 protein, human; D051376:Actin-Related Protein 2-3 Complex; C548234:MIRN133 microRNA, human; D035683:MicroRNAs