title: Tumor-suppressive microRNA-29s inhibit cancer cell migration and invasion via targeting LAMC1 in prostate cancer.
abstract: Our recent studies of microRNA (miRNA) expression signatures revealed that microRNA-29s (miR-29s; including miR-29a/b/c) were significantly downregulated in prostate cancer (PCa) and was a putative tumor-suppressive miRNA family in PCa. Herein, we aimed to investigate the functional significance of miR-29 in cancer cells and to identify novel miR-29s-mediated cancer pathways and target genes involved in PCa oncogenesis and metastasis. Restoration of miR-29s in PC3 and DU145 cell lines revealed significant inhibition of cancer cell migration and invasion. To identify miR-29s-mediated molecular pathways and targets, we used gene expression data and in silico database analysis. Our analysis demonstrated that miR-29s modulated the focal adhesion pathway. Moreover, the laminin γ1 (LAMC1) gene was a candidate target of miR-29s regulation. Luciferase reporter assays showed that miR-29s directly regulated LAMC1. Silencing of LAMC1 significantly inhibited cell migration and invasion in cancer cells, and LAMC1 was upregulated in PCa. miR-29s acted as tumor suppressors, contributing to cancer cell migration and invasion and directly targeting laminin signaling. Recognition of tumor-suppressive miRNA-mediated cancer pathways provides new insights into the potential mechanisms of PCa oncogenesis and metastasis, and suggests novel therapeutic strategies for treating this disease.
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Nishikawa
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Department of Urology, Teikyo University Chiba Medical Center, Chiba, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Kojima
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Enokida
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Chiyomaru
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sakamoto
authors.affiliation: Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Fuse
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Department of Urology, Teikyo University Chiba Medical Center, Chiba, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Naya
authors.affiliation: Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ichikawa
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D007797:Laminin; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; C089141:laminin gamma 1