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靶向乳腺癌中的 miR-205。

Targeting miR-205 in breast cancer.

机构信息

Southern Illinois University School of Medicine, Department of Medical Microbiology, Immunology and Cell Biology, 825 N. Rutledge, PO Box 19626, Springfield, IL 62794, USA.

出版信息

Expert Opin Ther Targets. 2009 Dec;13(12):1439-48. doi: 10.1517/14728220903338777.

Abstract

As small non-coding regulatory RNAs, microRNAs are capable of silencing gene expression by translational repression or mRNA degradation. Accumulating evidence indicates that deregulation of microRNAs is often associated with human malignancies and suggests a causal role of microRNAs in neoplasia, presumably because microRNAs can function as oncogenes or tumor suppressors. Among them, miR-205 is significantly underexpressed in breast tumors compared with matched normal breast tissue although miR-205 has been shown to be upregulated in some other type of tumors. Furthermore, breast cancer cell lines, including MCF-7 and MDA-MB-231, express a lower level of miR-205 than the non-malignant MCF-10A cells. Ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage-independent growth as well as cell invasion. These findings establish the tumor suppressive role of miR-205, which is probably through direct targeting of oncogenes such as ErbB3 and Zeb1. Therefore, miR-205 may serve as a unique therapeutic target for breast cancer.

摘要

作为小型非编码调控 RNA,microRNAs 能够通过翻译抑制或 mRNA 降解来沉默基因表达。越来越多的证据表明,microRNAs 的失调通常与人类恶性肿瘤有关,并表明 microRNAs 在肿瘤发生中起因果作用,这可能是因为 microRNAs 可以作为癌基因或肿瘤抑制因子发挥作用。其中,miR-205 在乳腺癌肿瘤组织中的表达明显低于匹配的正常乳腺组织,尽管已经表明在一些其他类型的肿瘤中 miR-205 被上调。此外,乳腺癌细胞系,包括 MCF-7 和 MDA-MB-231,表达的 miR-205 水平低于非恶性 MCF-10A 细胞。miR-205 的异位表达显著抑制细胞增殖、非锚定依赖性生长和细胞侵袭。这些发现确立了 miR-205 的肿瘤抑制作用,这可能是通过直接靶向癌基因如 ErbB3 和 Zeb1 实现的。因此,miR-205 可能成为乳腺癌的独特治疗靶点。

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