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miR-29b 调控人乳腺癌细胞的迁移。

miR-29b regulates migration of human breast cancer cells.

机构信息

School of Life Science, NJU 3 M Laboratory, Jiangsu Diabetes Research Center, Nanjing, Jiangsu, China.

出版信息

Mol Cell Biochem. 2011 Jun;352(1-2):197-207. doi: 10.1007/s11010-011-0755-z. Epub 2011 Feb 26.

Abstract

microRNAs (miRNAs) are short non-coding RNAs that regulate gene expression by targeting mRNAs, inhibiting the expression of the associated proteins. Although a role for aberrant miRNA expression in cancer has been postulated, the pathophysiologic role and relevance of aberrantly expressed miRNAs in tumor biology has not been established. We evaluated the expression pattern of miRNAs in human breast cancer cells by qPCR, finding out an up-regulated miRNA miR-29b and studying its biological effect by migration assay. We defined a target gene PTEN by bioinformatics approach and western blot. In breast cancer cell line MDA-MB-231 cell, which migrate faster than MCF-7, we observed that miR-29b was highly over-expressed. Inhibition of miR-29b in cultured cells increased the expression of the phosphatase and tensin homolog (PTEN) tumor suppressor, promoting apoptosis, decreasing migration, and decreasing invasion. In contrast, enhanced miR-29b expression by transfection with pre-miR-29b decreased the expression of PTEN and impaired apoptosis, increasing tumor cell migration and invasion. Moreover, PTEN was shown to be a direct target of miR-29b and was also shown to contribute to the miR-29b-mediated effects on cell invasion. Modulation of miR-29b altered the role of PTEN involved in cell migration and invasion. Aberrant expression of miR-29b, which modulates PTEN expression, can contribute to migration, invasion, and anti-apoptosis.

摘要

microRNAs (miRNAs) 是短的非编码 RNA,通过靶向 mRNAs 来调节基因表达,抑制相关蛋白质的表达。尽管已经提出了异常 miRNA 表达在癌症中的作用,但异常表达的 miRNAs 在肿瘤生物学中的病理生理作用和相关性尚未确定。我们通过 qPCR 评估了人乳腺癌细胞中 miRNAs 的表达模式,发现上调的 miRNA miR-29b,并通过迁移实验研究其生物学效应。我们通过生物信息学方法和 Western blot 定义了一个靶基因 PTEN。在 MDA-MB-231 细胞系中,该细胞系比 MCF-7 迁移更快,我们观察到 miR-29b 高度过表达。在培养细胞中抑制 miR-29b 会增加磷酸酶和张力蛋白同源物 (PTEN) 肿瘤抑制因子的表达,促进细胞凋亡,减少迁移和侵袭。相比之下,通过转染 pre-miR-29b 增强 miR-29b 的表达会降低 PTEN 的表达并损害细胞凋亡,增加肿瘤细胞的迁移和侵袭。此外,PTEN 被证明是 miR-29b 的直接靶标,并有助于 miR-29b 对细胞侵袭的调节作用。miR-29b 的调节改变了 PTEN 在细胞迁移和侵袭中所起的作用。miR-29b 的异常表达,调节了 PTEN 的表达,可以促进迁移、侵袭和抗凋亡。

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