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Int J Oncol. 2014 Jul;45(1):401-10. doi: 10.3892/ijo.2014.2437. Epub 2014 May 9.

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

Author information

1
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
2
Department of Urology, Teikyo University Chiba Medical Center, Chiba, Japan.
3
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
4
Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.

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.

PMID:
24820027
DOI:
10.3892/ijo.2014.2437
[Indexed for MEDLINE]

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