title: Overexpression of USP39 predicts poor prognosis and promotes tumorigenesis of prostate cancer via promoting EGFR mRNA maturation and transcription elongation.
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.
authors.affiliation: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.|The 2nd Department of Oncology of Chenggong Hospital, Xiamen University, Xiamen, 361003, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.|Department of Urinary Surgery of Third Affiliated Hospital, Second Military Medical University, Shanghai, 201805, China.
authors.forename: Xiu-Wu
authors.initials: XW
authors.lastname: Pan
authors.affiliation: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.affiliation: R & D Departmemt of DuruoBiotechnologies Inc., Shanghai, 200233, China.
authors.forename: Jian-Lei
authors.initials: JL
authors.lastname: Lu
authors.affiliation: R & D Departmemt of DuruoBiotechnologies Inc., Shanghai, 200233, China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Zhu
authors.affiliation: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Qi-Wei
authors.initials: QW
authors.lastname: Yang
authors.affiliation: Department of Urinary Surgery of Third Affiliated Hospital, Second Military Medical University, Shanghai, 201805, China.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Ye
authors.affiliation: Department of Urinary Surgery of Third Affiliated Hospital, Second Military Medical University, Shanghai, 201805, China.
authors.forename: Si-Shun
authors.initials: SS
authors.lastname: Gan
authors.affiliation: Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Lin-Hui
authors.initials: LH
authors.lastname: Wang
authors.affiliation: R & D Departmemt of DuruoBiotechnologies Inc., Shanghai, 200233, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Urinary Surgery of Ruijin Hospital, Shanghai Jiaotong University, Shanghai, 200025, China.
authors.forename: Dan-Feng
authors.initials: DF
authors.lastname: Xu
authors.affiliation: Department of Urinary Surgery of Third Affiliated Hospital, Second Military Medical University, Shanghai, 201805, China.
authors.forename: Xin-Gang
authors.initials: XG
authors.lastname: Cui
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D012333:RNA, Messenger; D012372:ROC Curve; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic; D064570:Ubiquitin-Specific Proteases / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C512478:EGFR protein, human; D066246:ErbB Receptors; C579218:USP39 protein, human; D064570:Ubiquitin-Specific Proteases
keywords: EGFR; USP39; prognosis; prostate cancer; tumorigenesis