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PPP5C通过调节JNK和ERK1/2磷酸化促进人前列腺癌细胞的增殖和存活。

PPP5C promotes cell proliferation and survival in human prostate cancer by regulating of the JNK and ERK1/2 phosphorylation.

作者信息

Lv Jian-Min, Chen Lu, Gao Yi, Huang Hai, Pan Xiu-Wu, Liu Xi, Chen Ming, Qu Fa-Jun, Li Lin, Wang Jun-Kai, Cui Xin-Gang, Xu Dan-Feng

机构信息

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

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

出版信息

Onco Targets Ther. 2018 Sep 12;11:5797-5809. doi: 10.2147/OTT.S161280. eCollection 2018.

Abstract

BACKGROUND

Prostate cancer (PCa) is one of the most common malignancies and a major leading cause of cancer-related deaths in males. And it is necessary to explore new molecular targets to enhance diagnosis and treatment level of the PCa. Serine/threonine protein phosphatase 5 (PPP5C) is a vital molecule that Involve in complex cell physiological activity.

PURPOSE

The objective of this study was to detecte the expression level of PPP5C in the tissue of prostate cancer patients and further discussed the PPP5C biological function and mechanisms on the PCa.

METHODS

The expression level of PPP5C was analyzed by immunohistochemistry and ONCOM-INE datasets. Lentivirus-mediated short hairpin RNA (shRNA) was constructed to silence the expression of PPP5C in prostate cancer cell. Cell viability and proliferation were measured using MTT and colony formation, and the cell cycle and apoptosis was analyszed by flow cytometry. The changes of downstream protein level and protein phosphorylation level were detected by western blot.

RESULTS

PPP5C was highly expressed in PCa tissue as analyzed by immunohistochemistry and ONCOMINE datasets. PPP5C Knockdown inhibited cell proliferation and colony formation in PCa cells. Flow cytometry analysis showed that DU145, PC3 and 22RV1 PCa cells deprived of PPP5C were arrested in G0/G1 phase and became apoptotic. Western blot analysis indicated that PPP5C knockdown could promote JNK and ERK phosphorylation.

CONCLUSION

Our study indicated that the PPP5C may become a new potential diagnostic biomarker and therapeutic target for the PCa.

摘要

背景

前列腺癌(PCa)是最常见的恶性肿瘤之一,也是男性癌症相关死亡的主要原因。因此,有必要探索新的分子靶点以提高前列腺癌的诊断和治疗水平。丝氨酸/苏氨酸蛋白磷酸酶5(PPP5C)是参与复杂细胞生理活动的重要分子。

目的

本研究旨在检测前列腺癌患者组织中PPP5C的表达水平,并进一步探讨PPP5C在前列腺癌中的生物学功能及机制。

方法

采用免疫组织化学和ONCOM-INE数据集分析PPP5C的表达水平。构建慢病毒介导的短发夹RNA(shRNA)以沉默前列腺癌细胞中PPP5C的表达。使用MTT和集落形成实验检测细胞活力和增殖情况,通过流式细胞术分析细胞周期和凋亡情况。采用蛋白质免疫印迹法检测下游蛋白水平和蛋白磷酸化水平的变化。

结果

免疫组织化学和ONCOMINE数据集分析显示,PPP5C在前列腺癌组织中高表达。敲低PPP5C可抑制前列腺癌细胞的增殖和集落形成。流式细胞术分析表明,缺失PPP5C的DU145、PC3和22RV1前列腺癌细胞停滞在G0/G1期并发生凋亡。蛋白质免疫印迹分析表明,敲低PPP5C可促进JNK和ERK磷酸化。

结论

我们的研究表明,PPP5C可能成为前列腺癌新的潜在诊断生物标志物和治疗靶点。

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