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Int J Oncol. 2016 Jul;49(1):111-22. doi: 10.3892/ijo.2016.3522. Epub 2016 May 16.

Direct regulation of LAMP1 by tumor-suppressive microRNA-320a in prostate cancer.

Author information

1
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
2
Department of Urology, Teikyo University Chiba Medical Centre, Chiba 299-0111, Japan.
3
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
4
Department of Urology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.

Abstract

Advanced prostate cancer (PCa) metastasizes to bone and lymph nodes, and currently available treatments cannot prevent the progression and metastasis of the disease. Therefore, an improved understanding of the molecular mechanisms of the progression and metastasis of advanced PCa using current genomic approaches is needed. Our miRNA expression signature in castration-resistant prostate cancer (CRPC) revealed that microRNA-320a (miR‑320a) was significantly reduced in cancer tissues, suggesting that miR‑320a may be a promising anticancer miRNA. The aim of this study was to investigate the functional roles of miR‑320a in naïve PCa and CRPC cells and to identify miR‑320a-regulated genes involved in PCa metastasis. The expression levels of miR‑320a were significantly reduced in naïve PCa, CRPC specimens, and PCa cell lines. Restoration of mature miR‑320a in PCa cell lines showed that miR‑320a significantly inhibited cancer cell migration and invasion. Moreover, we found that lysosomal-associated membrane protein 1 (LAMP1) was a direct target of miR‑320a in PCa cells. Silencing of LAMP1 using siRNA significantly inhibited cell proliferation, migration, and invasion in PCa cells. Overexpression of LAMP1 was observed in PCa and CRPC clinical specimens. Moreover, downstream pathways were identified using si-LAMP1-transfected cells. The discovery of tumor-suppressive miR‑320a-mediated pathways may provide important insights into the potential mechanisms of PCa metastasis.

PMID:
27212625
PMCID:
PMC4902064
DOI:
10.3892/ijo.2016.3522
[Indexed for MEDLINE]
Free PMC Article

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