Oncotarget

Research Papers:

Overexpression of USP39 predicts poor prognosis and promotes tumorigenesis of prostate cancer via promoting EGFR mRNA maturation and transcription elongation

Yi Huang, Xiu-Wu Pan, Lin Li, Lu Chen, Xi Liu, Jian-Lei Lu, Xiao-Mei Zhu, Hai Huang, Qi-Wei Yang, Jian-Qing Ye, Si-Shun Gan, Lin-Hui Wang, Yi Hong, Dan-Feng Xu and Xin-Gang Cui _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2016; 7:22016-22030. https://doi.org/10.18632/oncotarget.7882

Metrics: PDF 2652 views  |   HTML 2830 views  |   ?  


Abstract

Yi Huang1,2,*, Xiu-Wu Pan1,3,*, Lin Li1, Lu Chen1, Xi Liu1, Jian-Lei Lu4, Xiao-Mei Zhu4, Hai Huang1, Qi-Wei Yang1, Jian-Qing Ye3, Si-Shun Gan3, Lin-Hui Wang1, Yi Hong4, Dan-Feng Xu5, Xin-Gang Cui3

1Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China

2The 2nd Department of Oncology of Chenggong Hospital, Xiamen University, Xiamen, 361003, China

3Department of Urinary Surgery of Third Affiliated Hospital, Second Military Medical University, Shanghai, 201805, China

4R & D Departmemt of DuruoBiotechnologies Inc., Shanghai, 200233, China

5Department of Urinary Surgery of Ruijin Hospital, Shanghai Jiaotong University, Shanghai, 200025, China

*These authors have contributed equally to this work

Correspondence to:

Xin-Gang Cui, e-mail: [email protected]

Dan-Feng Xu, e-mail: [email protected]

Yi Hong, e-mail: [email protected]

Keywords: USP39, prostate cancer, prognosis, tumorigenesis, EGFR

Received: January 15, 2016    Accepted: February 23, 2016    Published: March 03, 2016

ABSTRACT

Castration resistance is a serious problem facing clinical treatment of prostate cancer (PCa). The underlying molecular mechanisms of acquired proliferation ability of tumor cells upon androgen deprivation are largely undetermined. In the present study, we identified that ubiquitin specific peptidase 39 (USP39) was significantly upregulated in PCa samples and cell lines. Elevated USP39 expression was positively correlated with Gleason score, predicted a poor outcome, and functioned as an independent risk factor for biochemical recurrence (BCR) especially in patients with a Gleason score ≤7. Our cell-based study showed that the expression level of USP39 was the highest in AR-negative PCa cell lines. Knockdown of USP39 in PCa cells inhibited cancer colony formation and tumor cell growth, and induced G2/M arrest and cell apoptosis. Microarray analysis suggested that knockdown of USP39 caused a reduced expression of EGFR. Silencing of USP39 inhibited the expression of EGFR 3′-end, and presented a remarkable block to the maturation of EGFR mRNA, suggesting that silencing of USP39 decreased the transcriptional elongation and maturation of EGFR mRNA. Oncomine datasets analysis showed that USP39 expression was positively correlated with EGFR level. The above findings suggest that USP39 plays a vital oncogenic role in the tumorigenesis of PCa and may prove to be a potential biomarker for predicting the prognosis of PCa patients.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 7882