The RNA-binding protein HuR in human cancer: A friend or foe?

The RNA-binding protein HuR in human cancer: A friend or foe?
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DOI:
10.1016/j.addr.2022.114179
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发表时间:
2022-05
影响因子:
16.1
通讯作者:
--
中科院分区:
医学1区
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--
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RNA结合蛋白(RBP)是与mRNAs中存在的特定顺式元件相关的关键反式因子,其稳定性和翻译受调控。RBP Hu抗原R(HUR)在多种人类癌症中过度表达,是临床预后不良的一个预后因素。HUR通过与与不同癌症特征和治疗抵抗有关的致癌mRNA子集相互作用来促进肿瘤发生。在小鼠异种移植模型中,降低癌细胞中的HUR水平导致肿瘤消退。这些发现催生了一种工作模型,在该模型中,癌细胞使用Hur(多个致癌mRNAs的主开关)来驱动耐药性,促进细胞存活和转移,从而使细胞质HUR高的肿瘤细胞更具进展性和抗药性。本文综述了HUR在癌症和其他疾病中的作用,HUR抑制的治疗潜力,以及HUR的药物发现现状。
The RNA-binding proteins (RBPs) are critical trans factors that associate with specific cis elements present in mRNAs whose stability and translation are subject to regulation. The RBP Hu antigen R (HuR) is overexpressed in a wide variety of human cancers and serves as a prognostic factor of poor clinical outcome. HuR promotes tumorigenesis by interacting with a subset of oncogenic mRNAs implicated in different cancer hallmarks, and resistance to therapy. Reduction of HuR levels in cancer cells leads to tumor regression in mouse xenograft models. These findings prompt a working model whereby cancer cells use HuR, a master switch of multiple oncogenic mRNAs, to drive drug resistance and promote cell survival and metastasis, thus rendering the tumor cells with high cytoplasmic HuR more progressive and resistant to therapy. This review summarizes the roles of HuR in cancer and other diseases, therapeutic potential of HuR inhibition, and the current status of drug discovery on HuR.
DOI: 10.1038/onc.2015.325
发表时间: 2016-05
期刊: Oncogene
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