miR-1207-3p regulates the androgen receptor in prostate cancer via FNDC1/fibronectin

Dibash K. Das, Michelle Naidoo, Adeodat Ilboudo, Jong Y. Park, Thahmina Ali, Konstantinos Krampis, Brian D. Robinson, Joseph R. Osborne, Olorunseun O. Ogunwobi

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Prostate cancer (PCa) is frequently diagnosed in men, and dysregulation of microRNAs is characteristic of many cancers. MicroRNA-1207-3p is encoded at the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of microRNA-1207-3p in PCa is unclear. We discovered that microRNA-1207-3p is significantly underexpressed in PCa cell lines in comparison to normal prostate epithelial cells. Increased expression of microRNA-1207-3p in PCa cells significantly inhibits proliferation, migration, and induces apoptosis via direct molecular targeting of FNDC1, a protein which contains a conserved protein domain of fibronectin (FN1). FNDC1, FN1, and the androgen receptor (AR) are significantly overexpressed in PCa cell lines and human PCa, and positively correlate with aggressive PCa. Prostate tumor FN1 expression in patients that experienced PCa-specific death is significantly higher than in patients that remained alive. Furthermore, FNDC1, FN1 and AR are concomitantly overexpressed in metastatic PCa. Consequently, these studies have revealed a novel microRNA-1207-3p/FNDC1/FN1/AR regulatory pathway in PCa.

Original languageEnglish
Pages (from-to)190-200
Number of pages11
JournalExperimental Cell Research
Volume348
Issue number2
DOIs
StatePublished - 1 Nov 2016
Externally publishedYes

Keywords

  • Androgen receptor
  • Fibronectin
  • Fibronectin type III domain containing 1
  • MiR-1207-3p
  • Prostate cancer

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