4.5 Article

miR-205 is frequently downregulated in prostate cancer and acts as a tumor suppressor by inhibiting tumor growth

Journal

ASIAN JOURNAL OF ANDROLOGY
Volume 15, Issue 6, Pages 735-741

Publisher

WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.1038/aja.2013.80

Keywords

c-SRC; miR-205; prostate cancer (PCa); tumor growth

Funding

  1. Program for Development of Innovative Research Team in the First Affiliated Hospital of Nanjing Medical University [81171963]
  2. National Nature Science Foundation of China [81272831/H1619]
  3. Natural Science Foundation of Jiangsu Province [BK2010577]
  4. Jiangsu Province's Outstanding Medical Academic Leader program [RC201178]
  5. Provincial Initiative Program for Excellency Disciplines

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The purpose of this study was to elucidate the molecular mechanisms of microRNA-205 (miR-205) as a tumor suppressor in prostate cancer (PCa). In the present study, microRNA microarray analysis suggested that the expression of miR-205 was significantly decreased in advanced PCa compared with early PCa. Real-time PCR analysis also indicated that miR-205 expression was significantly decreased in PCa tissues compared with non-cancerous tissues. Moreover, the expression of miR-205 has been demonstrated to be associated with the clinicopathological stage and total/free prostate-specific antigen (PSA) level of PCa. Functional analyses showed that both the overexpression of miR-205 and the knockdown of c-SRC in PCa cell lines could inhibit cell growth, colony formation, migration, invasion and the cell cycle as well as induce cell apoptosis in vitro. Furthermore, over-expressing miR-205 reduced tumorigenicity in vivo. Through a luciferase activity assay and Western blotting, c-SRC was identified as a target of miR-205 in cells. The overexpression of miR-205 suppressed c-SRC and its downstream signaling molecules, including FAK, p-FAK, ERK1/2 and p-ERK1/2, and attenuated cell proliferation, invasion and tumor growth.

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