Elevated miR-615-3p Expression Predicts Adverse Clinical Outcome and Promotes Proliferation and Migration of Prostate Cancer Cells

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  • Emma B Laursen
  • Jacob Fredsøe
  • Linnéa Schmidt
  • ,
  • Siri Strand
  • Helle Kristensen, Exiqon A/S, Vedbaek, Denmark
  • ,
  • Anne K Ildor Rasmussen, Exiqon A/S, Vedbaek, Denmark
  • ,
  • Tina F Daugaard
  • Peter Mouritzen, Exiqon A/S, Vedbaek, Denmark
  • ,
  • Søren Høyer
  • ,
  • Gitte Kristensen, University of Copenhagen
  • ,
  • Hein V Stroomberg, University of Copenhagen
  • ,
  • Klaus Brasso, University of Copenhagen
  • ,
  • Martin A Røder, University of Copenhagen
  • ,
  • Michael Borre
  • Karina D Sørensen

miR-615-3p has previously been described as up-regulated in prostate cancer (PC) tissue samples compared with nonmalignant controls; however, its prognostic potential and functional role in PC remain largely unknown. In this study, we investigated the clinical and biological relevance of miR-615-3p in PC. The expression of miR-615-3p was measured in PC tissue specimens from 239 men who underwent radical prostatectomy (RP), and it was investigated if miR-615-3p could predict postoperative biochemical recurrence (BCR). These findings were subsequently validated in three independent RP cohorts (n = 222, n = 273, and n = 387) and functional overexpression studies conducted in PC cells (PC3M). High miR-615-3p expression was significantly associated with BCR in four independent PC patient cohorts (P < 0.05, log-rank test). In addition, high miR-615-3p expression was a significant predictor of PC-specific survival in univariate (hazard ratio, 3.75; P < 0.001) and multivariate (hazard ratio, 2.66; P = 0.008) analysis after adjustment for the CAPRA-S nomogram in a merged RP cohort (N = 734). Moreover, overexpression of miR-615-3p in PC cells (PC3M) significantly increased cell viability, proliferation, apoptosis, and migration. Together, our results suggest that miR-615-3p is a significant predictor of postoperative BCR and PC-specific survival and has oncogenic functions in PC cells.

Original languageEnglish
JournalThe American Journal of Pathology
Volume189
Issue12
Pages (from-to)2377-2388
Number of pages12
ISSN0002-9440
DOIs
Publication statusPublished - Dec 2019

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