MicroRNA-125a represses cell growth by targeting HuR in breast cancer.
MicroRNA-125a represses cell growth by targeting HuR in breast cancer.
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DOI：
10.4161/rna.6.5.10079
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发表时间：
2009-11
期刊：
影响因子：
4.1
通讯作者：
Hartley RS
中科院分区：
文献类型：
--
作者：
Guo X;Wu Y;Hartley RS
MicroRNA（miRNAs）是一类天然存在的小的非编码RNA，其在发育、正常细胞功能和疾病期间控制基因表达。虽然有新的证据表明，一些miRNA可以作为致癌基因或肿瘤抑制因子，但对miRNA在癌症中的作用的理解有限。在这项研究中，我们观察到miR-125 a的表达与HuR在几种不同的乳腺癌细胞系中的表达呈负相关。HuR是一种应激诱导的RNA结合蛋白，其表达在几种不同的癌症中升高或定位扰动。HuR细胞质定位增加是乳腺癌的预后标志物。真实的时间PCR和基因报告分析表明，HuR被miR-125 a抑制。在乳腺癌细胞中重新建立miR-125 a表达降低了HuR蛋白水平并抑制了细胞生长。使用MCF-7乳腺癌细胞，我们进一步阐明了miR-125 a通过显著抑制细胞增殖和促进细胞凋亡来抑制细胞生长。此外，miR-125 a过表达也抑制了细胞迁移。重要的是，由miR-125 a引起的细胞增殖和迁移的抑制部分被HuR再表达所挽救。我们的研究结果表明，miR-125 a可能作为乳腺癌的肿瘤抑制因子，HuR作为直接和功能性靶点。
MicroRNAs (miRNAs) are a class of naturally occurring, small, non-coding RNAs that control gene expression during development, normal cell function, and disease. Although there is emerging evidence that some miRNAs can function as oncogenes or tumor suppressors, there is limited understanding of the role of miRNAs in cancer. In this study, we observed that the expression of miR-125a was inversely correlated with HuR expression in several different breast carcinoma cell lines. HuR is a stress-induced RNA binding protein whose expression is elevated or localization perturbed in several different cancers. Increased cytoplasmic localization of HuR is a prognostic marker in breast cancer. Real time PCR and gene reporter assays indicated that HuR was translationally repressed by miR-125a. Re-establishing miR-125a expression in breast cancer cells decreased HuR protein level and inhibited cell growth. Using MCF-7 breast cancer cells, we further clarified that miR-125a inhibited cell growth via a dramatic suppression of cell proliferation and promotion of apoptosis. In addition, cell migration was also inhibited by miR-125a overexpression. Importantly, the repression of cell proliferation and migration engendered by miR-125a was partly rescued by HuR re-expression. Our results suggest that miR-125a may function as a tumor suppressor for breast cancer, with HuR as a direct and functional target.
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影响因子：
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通讯作者：
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