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姜黄素通过调节DLK1-DIO3印记基因簇微小RNA抑制人前列腺癌干细胞的体外增殖和侵袭。

Curcumin Suppresses In Vitro Proliferation and Invasion of Human Prostate Cancer Stem Cells by Modulating DLK1-DIO3 Imprinted Gene Cluster MicroRNAs.

作者信息

Zhang Hu, Zheng Jiajia, Shen Hongliang, Huang Yongyi, Liu Te, Xi Hao, Chen Chuan

机构信息

1 Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine , Shanghai, China .

2 Department of Urology, Beijing Friendship Hospital , Capital Medical University, Beijing, China .

出版信息

Genet Test Mol Biomarkers. 2018 Jan;22(1):43-50. doi: 10.1089/gtmb.2017.0179. Epub 2017 Nov 27.

Abstract

AIMS

Curcumin can suppress human prostate cancer (HuPCa) cell proliferation and invasion. However, it is not known whether curcumin can inhibit HuPCa stem cell (HuPCaSC) proliferation and invasion.

MATERIALS AND METHODS

We used methyl thiazolyl tetrazolium and Transwell assays to examine the proliferation and invasion of the HuPCaSC lines DU145 and 22Rv1 following curcumin or dimethyl sulfoxide (control) treatment. The microRNA (miRNA) expression levels in the DLK1-DIO3 imprinted genomic region in the cells and in tumor tissues from patients with PCa were examined using microarray and quantitative PCR.

RESULTS

The median inhibitory concentration of curcumin for HuPCa cells significantly inhibited HuPCaSC proliferation and invasion in vitro. The miR-770-5p and miR-1247 expression levels in the DLK1-DIO3 imprinted gene cluster were significantly different between the curcumin-treated and control HuPCaSCs. Overexpression of these positive miRNAs significantly increased the inhibition rates of miR-770-5p- and miR-1247-transfected HuPCaSCs compared to the control miR-Mut-transfected HuPCaSCs. Lastly, low-tumor grade PCa tissues had higher miR-770-5p and miR-1247 expression levels than high-grade tumor tissues.

CONCLUSIONS

Curcumin can suppress HuPCaSC proliferation and invasion in vitro by modulating specific miRNAs in the DLK1-DIO3 imprinted gene cluster.

摘要

目的

姜黄素可抑制人前列腺癌细胞(HuPCa)的增殖和侵袭。然而,尚不清楚姜黄素是否能抑制HuPCa干细胞(HuPCaSC)的增殖和侵袭。

材料与方法

我们使用甲基噻唑基四氮唑蓝和Transwell实验检测姜黄素或二甲基亚砜(对照)处理后HuPCaSC系DU145和22Rv1的增殖和侵袭情况。使用微阵列和定量PCR检测细胞及前列腺癌患者肿瘤组织中DLK1 - DIO3印记基因组区域的微小RNA(miRNA)表达水平。

结果

姜黄素对HuPCa细胞的半数抑制浓度显著抑制了HuPCaSC在体外的增殖和侵袭。在经姜黄素处理和对照的HuPCaSC之间,DLK1 - DIO3印记基因簇中的miR - 770 - 5p和miR - 1247表达水平存在显著差异。与对照miR - Mut转染的HuPCaSC相比,这些正向miRNA的过表达显著提高了miR - 770 - 5p和miR - 1247转染的HuPCaSC的抑制率。最后,低肿瘤分级的前列腺癌组织比高分级肿瘤组织具有更高的miR - 770 - 5p和miR - 1247表达水平。

结论

姜黄素可通过调节DLK1 - DIO3印记基因簇中的特定miRNA来抑制HuPCaSC在体外的增殖和侵袭。

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