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

Oncogene volume 38, pages 4820–4834 (2019)Cite this article

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Abstract

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.

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Acknowledgements

We thank Dr. Donald L Hill for editorial assistance in preparing this manuscript. This work was supported by grants from the National Institutes of Health/National Cancer Institute (CA118948, CA179282, and CA013148 to LW and RL), the Department of Defense (BC160808, PC130594, and PC140308 to LW and RL), the Mike Slive Foundation for Prostate Cancer Research (to LW), and the Natural Science Foundation of China (Nos. 31571126, 31571342, and 81772757 to XL, BL, and RC). Results are based, in part, on data generated by the TCGA Research Network: http://cancergenome.nih.gov/.

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  1. These authors contributed equally: Yicun Wang, Xin Li

Authors and Affiliations

  1. Provincial Key Laboratory on Molecular and Chemical Genetics, Second Hospital of Jilin University, Changchun, China

    Yicun Wang, Xin Li, Wei Liu, Bingjin Li & Ranji Cui

  2. Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA

    Yicun Wang, Xin Li, Wei Liu, Fengping Hu, Lizhong Wang & Runhua Liu

  3. Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Dongquan Chen

  4. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA

    Dongquan Chen, Lizhong Wang & Runhua Liu

  5. Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA

    Xiaoguang M. Liu

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All authors read and approved the final manuscript. RL and RC designed the studies; YW, WL, XL, XML, RL, and LW carried out the experiments; RL, BL, YW, and LW wrote the manuscript; and LW, YW, BL, XL, XML, RC, and RL performed data analysis.

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Wang, Y., Li, X., Liu, W. et al. MicroRNA-1205, encoded on chromosome 8q24, targets EGLN3 to induce cell growth and contributes to risk of castration-resistant prostate cancer. Oncogene 38, 4820–4834 (2019). https://doi.org/10.1038/s41388-019-0760-3

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