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微小RNA-124调节转化生长因子-α诱导的人前列腺癌细胞上皮-间质转化。

MicroRNA-124 regulates TGF-α-induced epithelial-mesenchymal transition in human prostate cancer cells.

作者信息

Qin Wei, Pan Yujia, Zheng Xiulan, Li Dong, Bu Jingyi, Xu Chunyan, Tang Jiebing, Cui Rongjun, Lin Ping, Yu Xiaoguang

机构信息

Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.

Department of Ultrasonography, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China.

出版信息

Int J Oncol. 2014 Sep;45(3):1225-31. doi: 10.3892/ijo.2014.2506. Epub 2014 Jun 19.

Abstract

Transforming growth factor-α (TGF-α) is upregulated in advanced stages of prostate cancer and strongly correlated with metastasis. However, the effect of TGF-α on epithelial-mesenchymal transition (EMT) in prostate cancer and the underlying mechanisms remain unclear. Recently, microRNAs have emerged as new regulators of EMT. This study found that treatment of DU145 cells with TGF-α suppressed the expression of epithelial marker E-cadherin and increased the expression of mesenchymal marker Vimentin as well as changed the cell morphology from cobblestone shape to spindle shape. The level of miR-124 was downregulated by TGF-α in several different cancer cell lines. Enforced expression of miR-124 abolished TGF-α-induced EMT. Slug was proven to be a target of miR-124 and mediated the inhibitory effect of miR-124 on TGF-α-induced EMT. Furthermore, overexpression of miR-124 reduced the migratory and invasive capacity of TGF-α-treated DU145 cells. In conclusion, our findings suggest that miR-124 inhibits TGF-α-induced EMT in DU145 cells by targeting Slug. Thus, miR-124 may be a potential target for prostate cancer therapeutic intervention.

摘要

转化生长因子-α(TGF-α)在前列腺癌晚期上调,且与转移密切相关。然而,TGF-α对前列腺癌上皮-间质转化(EMT)的影响及其潜在机制仍不清楚。最近,微小RNA已成为EMT的新调节因子。本研究发现,用TGF-α处理DU145细胞可抑制上皮标志物E-钙黏蛋白的表达,增加间质标志物波形蛋白的表达,并使细胞形态从鹅卵石样变为纺锤形。在几种不同的癌细胞系中,TGF-α可下调miR-124的水平。miR-124的强制表达消除了TGF-α诱导的EMT。已证实Slug是miR-124的靶标,并介导了miR-124对TGF-α诱导的EMT的抑制作用。此外,miR-124的过表达降低了TGF-α处理的DU145细胞的迁移和侵袭能力。总之,我们的研究结果表明,miR-124通过靶向Slug抑制TGF-α诱导的DU145细胞EMT。因此,miR-124可能是前列腺癌治疗干预的潜在靶点。

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