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HuR,一种关键的转录后调控因子,及其在乳腺癌进展中的意义。

HuR, a key post-transcriptional regulator, and its implication in progression of breast cancer.

机构信息

Department of Surgery, Cardiff University School of Medicine, Cardiff, UK.

出版信息

Histol Histopathol. 2010 Oct;25(10):1331-40. doi: 10.14670/HH-25.1331.

Abstract

HuR, an ubiquitously expressed member of the Hu family, selectively binds and stabilizes ARE-containing mRNAs encoding proto-oncogenes, cell cycle regulators, cytokines and growth factors. The mechanism of HuR stabilization on target mRNAs is believed to be mediated through competition with destabilizing ARE-BPs. HuR is mainly localized within the cell nucleus and the nucleo-cytoplasmic shuttling of HuR is generally assumed as the initial and critical step of its stabilizing effects. A number of signaling pathways are believed to be involved in HuR shuttling. Due to the pivotal role played by HuR in stabilizing the mRNA of key factors or cytokines involved in carcinogenesis and subsequent progression, its implication and therapeutic potential in cancer have been investigated intensively since its discovery in 1996. This review discusses the role of HuR in the stabilization of key mRNAs and it's the nucleo-cytoplasmic shuttling. The review also covers the current knowledge of HuR's role in carcinogenesis, particularly its involvement in breast cancer, and the feasibility of using HuR as a therapeutic target for the treatment of breast cancer.

摘要

HuR 是 Hu 家族中普遍表达的成员,它选择性地结合并稳定含有 ARE 的 mRNA,这些 mRNA 编码原癌基因、细胞周期调节剂、细胞因子和生长因子。HuR 稳定靶 mRNA 的机制被认为是通过与不稳定的 ARE-BP 竞争介导的。HuR 主要定位于细胞核内,HuR 的核质穿梭通常被认为是其稳定作用的初始和关键步骤。许多信号通路被认为参与 HuR 穿梭。由于 HuR 在稳定参与致癌作用和随后进展的关键因子或细胞因子的 mRNA 中起着关键作用,自 1996 年发现以来,其在癌症中的意义和治疗潜力已被广泛研究。本文综述了 HuR 在稳定关键 mRNA 及其核质穿梭中的作用。还涵盖了 HuR 在致癌作用中的作用的最新知识,特别是其在乳腺癌中的参与,以及将 HuR 用作治疗乳腺癌的治疗靶点的可行性。

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