Tumor-suppressive microRNA-29s inhibit cancer cell migration and invasion via targeting LAMC1 in prostate cancer

Nishikawa,Rika; Goto,Yusuke; Kojima,Satoko; Enokida,Hideki; Chiyomaru,Takeshi; Kinoshita,Takashi; Sakamoto,Shinichi; Fuse,Miki; Nakagawa,Masayuki; Naya,Yukio; Ichikawa,Tomohiko; Seki,Naohiko

doi:10.3892/ijo.2014.2437

Tumor-suppressive microRNA-29s inhibit cancer cell migration and invasion via targeting LAMC1 in prostate cancer

Authors:
- Rika Nishikawa
- Yusuke Goto
- Satoko Kojima
- Hideki Enokida
- Takeshi Chiyomaru
- Takashi Kinoshita
- Shinichi Sakamoto
- Miki Fuse
- Masayuki Nakagawa
- Yukio Naya
- Tomohiko Ichikawa
- Naohiko Seki
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Affiliations: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan, Department of Urology, Teikyo University Chiba Medical Center, Chiba, Japan, Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan, Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan
Published online on: May 9, 2014 https://doi.org/10.3892/ijo.2014.2437
Pages: 401-410

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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.

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