MicroRNA-1205, encoded on chromosome 8q24, targets EGLN3 to induce cell growth and contributes to risk of castration-resistant prostate cancer

Academic Article

Abstract

  • © 2019, Springer Nature Limited. The chromosome 8q24.21 locus, which contains the proto-oncogene c-MYC, long non-coding RNA PVT1, and microRNAs (miRs), is the most commonly amplified region in human prostate cancer. A long-range interaction of genetic variants with c-MYC or long non-coding PVT1 at this locus contributes to the genetic risk of prostate cancer. At this locus is a cluster of genes for six miRs (miR-1204, -1205, -1206, -1207-3p, -1207-5p, and -1208), but their functional role remains elusive. Here the copy numbers and expression levels of miRs-1204–1208 were investigated using quantitative PCR for prostate cancer cell lines and primary tumors. The data revealed that copy numbers and expression of miR-1205 were increased in both castration-resistant prostate cancer cell lines and in primary tumors. In castration-resistant prostate cancer specimens, the copy number at the miR-1205 locus correlated with the expression of miR-1205. Furthermore, functional analysis with an miR-1205 mimic, an miR-1205 inhibitor, and CRISPR/Cas9 knockout revealed that, in human prostate cancer cells, miR-1205 promoted cell proliferation and cell cycle progression and inhibited hydrogen peroxide-induced apoptosis. In these cells, miR-1205 downregulated the expression of the Egl-9 family hypoxia inducible factor 3(EGLN3) gene and targeted a site in its 3′-untranslated region to downregulate its transcriptional activity. Thus, by targeting EGLN3, miR-1205 has an oncogenic role and may contribute to the genetic risk of castration-resistant prostate cancer.
  • Published In

  • Oncogene  Journal
  • Digital Object Identifier (doi)

    Author List

  • Wang Y; Li X; Liu W; Li B; Chen D; Hu F; Wang L; Liu XM; Cui R; Liu R
  • Start Page

  • 4820
  • End Page

  • 4834
  • Volume

  • 38
  • Issue

  • 24