title: Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma.
abstract: Our recent studies of microRNA (miRNA) expression signatures indicated that microRNA-29a (miR-29a) was significantly downregulated in several types of human cancers, suggesting that miR-29a may be a putative tumor-suppressive miRNA in human cancers. The aim of this study was to investigate the functional significance of miR-29a in cervical squamous cell carcinoma (SCC) and to identify novel miR-29a-regulated cancer pathways and target genes involved in cervical SCC oncogenesis and metastasis. Restoration of miR-29a in cervical cancer cell lines (CaSKi, HeLa, ME180 and Yumoto) revealed that this miRNA significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that heat-shock protein 47 (HSP47), a member of the serpin superfamily of serine proteinase inhibitors and a molecular chaperone involved in the maturation of collagen molecules, was a potential target of miR-29a regulation. Luciferase reporter assays showed that miR-29a directly regulated HSP47. Moreover, silencing of the HSP47 gene significantly inhibited cell migration and invasion in cancer cells and the expression of HSP47 was upregulated in cancer tissues and cervical intraepithelial neoplasia (CIN), as demonstrated by immunostaining. Downregulation of miR-29a was a frequent event in cervical SCC and miR-29a acted as a tumor suppressor by directly targeting HSP47. Recognition of tumor-suppressive miRNA-regulated molecular targets provides new insights into the potential mechanisms of cervical SCC oncogenesis and metastasis and suggests novel therapeutic strategies for treatment of this disease.
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Nijiro
authors.initials: N
authors.lastname: Nohata
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yoshino
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Itesako
authors.forename: Lisa
authors.initials: L
authors.lastname: Fujimura
authors.forename: Akira
authors.initials: A
authors.lastname: Mitsuhashi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Usui
authors.forename: Hideki
authors.initials: H
authors.lastname: Enokida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Makio
authors.initials: M
authors.lastname: Shozu
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D050958:HSP47 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D050958:HSP47 Heat-Shock Proteins; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; C494660:SERPINH1 protein, human