Overexpression of USP39 predicts poor prognosis and promotes tumorigenesis of prostate cancer via promoting EGFR mRNA maturation and transcription elongation.
Overexpression of USP39 predicts poor prognosis and promotes tumorigenesis of prostate cancer via promoting EGFR mRNA maturation and transcription elongation.
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DOI：
10.18632/oncotarget.7882
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发表时间：
2016-04-19
期刊：
影响因子：
--
通讯作者：
Cui XG
中科院分区：
文献类型：
--
作者：
Huang Y;Pan XW;Li L;Chen L;Liu X;Lu JL;Zhu XM;Huang H;Yang QW;Ye JQ;Gan SS;Wang LH;Hong Y;Xu DF;Cui XG
去势抵抗是前列腺癌临床治疗面临的严重问题。肿瘤细胞在雄激素剥夺后获得增殖能力的潜在分子机制在很大程度上尚未确定。在本研究中，我们确定了泛素特异性肽酶39（USP 39）在前列腺癌样品和细胞系中显著上调。USP 39表达升高与Gleason评分呈正相关，预测预后不良，并作为生化复发（BCR）的独立风险因素，尤其是在Gleason评分≤7的患者中。我们基于细胞的研究表明，USP 39的表达水平在AR阴性PCa细胞系中最高。在PCa细胞中敲低USP 39抑制癌集落形成和肿瘤细胞生长，并诱导G2/M期阻滞和细胞凋亡。微阵列分析表明，USP 39的敲低导致EGFR表达减少。USP 39基因的沉默可抑制EGFR 3′端的表达，并对EGFR mRNA的成熟有明显的阻滞作用，提示USP 39基因的沉默可降低EGFR mRNA的转录延长和成熟。Oncomine数据集分析显示USP 39表达与EGFR水平呈正相关。以上结果表明，USP 39在PCa的肿瘤发生中起着重要的致癌作用，并可能被证明是预测PCa患者预后的潜在生物标志物。
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.
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影响因子：
3.7
作者：
Koga M;Satoh T;Takasaki I;Kawamura Y;Yoshida M;Kaida D
通讯作者：
Kaida D
影响因子：
5.6
作者：
Spans L;Clinckemalie L;Helsen C;Vanderschueren D;Boonen S;Lerut E;Joniau S;Claessens F
通讯作者：
Claessens F
影响因子：
6.7
作者：
Pan Z;Pan H;Zhang J;Yang Y;Liu H;Yang Y;Huang G;Ni J;Huang J;Zhou W
通讯作者：
Zhou W
影响因子：
20.3
作者：
Cazzola, Mario;Rossi, Marianna;Malcovati, Luca
通讯作者：
Malcovati, Luca
影响因子：
1.6
作者：
Molitierno, Joseph;Evans, Aubrey;Pruthi, Raj S.
通讯作者：
Pruthi, Raj S.