Open Access

Significance of the TMPRSS2:ERG gene fusion in prostate cancer

  • Authors:
    • Zhu Wang
    • Yuliang Wang
    • Jianwen Zhang
    • Qiyi Hu
    • Fan Zhi
    • Shengping Zhang
    • Dengqi Mao
    • Ying Zhang
    • Hui Liang
  • View Affiliations

  • Published online on: August 18, 2017     https://doi.org/10.3892/mmr.2017.7281
  • Pages: 5450-5458
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The transmembrane protease serine 2:v‑ets erythroblastosis virus E26 oncogene homolog (TMPRSS2:ERG) gene fusion is common in prostate cancer, while its functional role is not fully understood. The present study aimed to investigate the significance of the TMPRSS2:ERG gene fusion in human prostate cancers using bioinformatics tools. Comprehensive alteration analysis of TMPRSS2 and ERG in 148 different human cancer studies was performed by cBioPortal, and the mRNA expression level of the ERG gene was evaluated using Oncomine analysis. Furthermore, lentiviral short hairpin (sh)RNA‑mediated knockdown of TMPRSS2:ERG was performed to study the impact of ERG silencing on cell proliferation and cell cycle distribution in prostate cancer cells. The results demonstrated that the TMPRSS2 and ERG genes were mostly altered in prostate cancer, and the most frequent alteration was gene fusion. Oncomine analysis demonstrated that the ERG gene was significantly upregulated in prostate clinical samples compared with the normal prostate gland in four independent datasets, and a positive association was observed between potassium inwardly‑rectifying channel subfamily J member 15, down syndrome critical region gene 4, potassium inwardly‑rectifying channel subfamily J member 6 and ERG gene expression. There were 272 mutations of the ERG gene identified in the cBioPortal database; among the mutations, 2 missense mutations (R367C and P401H) were regarded as functional mutations (functional impact score >1.938). Furthermore, the present study successfully knocked down ERG gene expression through a lentiviral‑mediated gene silencing approach in VCaP prostate cancer cells. The ERG mRNA and protein expression levels were both suppressed significantly, and a cell‑cycle arrest at G0/G1 phase was observed after ERG gene silencing. In conclusion, these bioinformatics analyses provide novel insights for TMPRSS2:ERG fusion gene study in prostate cancer. Target inhibition of ERG expression could significantly cause cell growth arrest in prostate cancer cells, which could be a potentially valuable target for prostate cancer treatment. However, the precise mechanism of these results remains unclear; therefore, further studies are required.

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October-2017
Volume 16 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
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Spandidos Publications style
Wang Z, Wang Y, Zhang J, Hu Q, Zhi F, Zhang S, Mao D, Zhang Y and Liang H: Significance of the TMPRSS2:ERG gene fusion in prostate cancer. Mol Med Rep 16: 5450-5458, 2017
APA
Wang, Z., Wang, Y., Zhang, J., Hu, Q., Zhi, F., Zhang, S. ... Liang, H. (2017). Significance of the TMPRSS2:ERG gene fusion in prostate cancer. Molecular Medicine Reports, 16, 5450-5458. https://doi.org/10.3892/mmr.2017.7281
MLA
Wang, Z., Wang, Y., Zhang, J., Hu, Q., Zhi, F., Zhang, S., Mao, D., Zhang, Y., Liang, H."Significance of the TMPRSS2:ERG gene fusion in prostate cancer". Molecular Medicine Reports 16.4 (2017): 5450-5458.
Chicago
Wang, Z., Wang, Y., Zhang, J., Hu, Q., Zhi, F., Zhang, S., Mao, D., Zhang, Y., Liang, H."Significance of the TMPRSS2:ERG gene fusion in prostate cancer". Molecular Medicine Reports 16, no. 4 (2017): 5450-5458. https://doi.org/10.3892/mmr.2017.7281