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.
Oncogene. 2019 Feb 26 [Epub ahead of print]
Yicun Wang, Xin Li, Wei Liu, Bingjin Li, Dongquan Chen, Fengping Hu, Lizhong Wang, Xiaoguang M Liu, Ranji Cui, Runhua Liu
Provincial Key Laboratory on Molecular and Chemical Genetics, Second Hospital of Jilin University, Changchun, China., Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA., Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA., Provincial Key Laboratory on Molecular and Chemical Genetics, Second Hospital of Jilin University, Changchun, China. ., Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA. .