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MicroRNA-588在人类前列腺癌中上调,具有预后和功能意义。

MicroRNA-588 is upregulated in human prostate cancer with prognostic and functional implications.

作者信息

Zhao Nan, Lin Tao, Zhao Changbo, Zhao Shikai, Zhou Shiming, Li Yuqiao

机构信息

Department of Andrology, Liaocheng People's Hospital, Liaocheng, 252000, China.

Department of Urology, Liaocheng People's Hospital, Liaocheng, 252000, China.

出版信息

J Cell Biochem. 2017 Oct 5. doi: 10.1002/jcb.26417.

DOI:10.1002/jcb.26417
PMID:28980707
Abstract

BACKGROUND

Epigenetic factors of microRNAs (miRNAs) are important biomarkers and modulators in human prostate cancer (PCa). In this work, we characterized the expression, biomarker-potential and functional regulation of miR-588 in PCa.

METHODS

Endogenous miR-588 levels were quantified by qRT-PCR in both prostate-specific antigen (PSA)-negative and PSA-positive PCa cell lines, as well as human PCa tumors. The associations between endogenous miR-588 and PCa patients' clinical outcomes and postoperative overall survival were statistically examined. Moreover, in both PSA-negative DU145 and PSA-positive LNCaP, downregulation of miR-588 was achived by transduction of miR-588 inhibitor lentivirus. The subsequent effects of miR-588 downregulation on PCa cell developments were investigated both in vitro and in vivo.

RESULTS

MiR-588 was profoundly upregulated in both PSA-negative and PSA-positive PCa cells, as well as in PCa tumors. Significant miR-588 upregulation was found to be closely associated with PCa patients' poor clinical outcomes and shorter postoperative overall survivals. In DU145 and LNCaP cell lines, lentiviral transduction markedly downregulated endogenous miR-588 levels. MiR-588 downregulation was shown to profoundly inhibit PCa proliferation in vitro and xenograft in vivo.

CONCLUSION

Aberrant upregulation of endogenous miR-588 in PCa patients may be a prognostic biomarker, indicative of their poor clinical outcomes. Inhibiting endogenous miR-588 may also serve as a therapeutic target for PCa treatment. This article is protected by copyright. All rights reserved.

摘要

背景

微小RNA(miRNA)的表观遗传因素是人类前列腺癌(PCa)的重要生物标志物和调节因子。在本研究中,我们对miR-588在PCa中的表达、生物标志物潜力及功能调控进行了表征。

方法

采用qRT-PCR对前列腺特异性抗原(PSA)阴性和PSA阳性的PCa细胞系以及人类PCa肿瘤中的内源性miR-588水平进行定量。对PCa患者的临床结局与内源性miR-588及术后总生存期之间的关联进行统计学检验。此外,在PSA阴性的DU145和PSA阳性的LNCaP细胞系中,通过转导miR-588抑制剂慢病毒实现miR-588的下调。在体外和体内研究了miR-588下调对PCa细胞发育的后续影响。

结果

miR-588在PSA阴性和PSA阳性的PCa细胞以及PCa肿瘤中均显著上调。发现miR-588的显著上调与PCa患者不良的临床结局和较短的术后总生存期密切相关。在DU145和LNCaP细胞系中,慢病毒转导显著下调了内源性miR-588水平。miR-588下调在体外显著抑制PCa增殖,在体内显著抑制异种移植瘤生长。

结论

PCa患者内源性miR-588的异常上调可能是一种预后生物标志物,表明其临床结局不佳。抑制内源性miR-588也可能成为PCa治疗的一个靶点。本文受版权保护。保留所有权利。

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