Understanding and targeting the disease-related RNA binding protein human antigen R (HuR)
Understanding and targeting the disease-related RNA binding protein human antigen R (HuR)
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DOI：
10.1002/wrna.1581
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发表时间：
2020-01-23
影响因子：
7.3
通讯作者：
Brody, Jonathan R.
中科院分区：
文献类型：
--
作者：
Schultz, Christopher W.;Preet, Ranjan;Brody, Jonathan R.
基因表达改变是许多疾病状态（如肿瘤发生）的特征，在大多数癌症中，它促进了癌细胞的生存和适应。全球基因表达的改变受到转录后基因调控的强烈影响。RNA结合蛋白（RBP） HuR （ELAVL1）是一种已知的转录后基因调控因子，在大多数人类癌症中过表达。在许多癌变情况下，HuR不仅过度表达，而且“过度活跃”，表现为细胞质内亚细胞定位增加。这种对HuR表达和细胞质定位的失调使HuR能够稳定和增加各种促生存信使RNA （mrna）的翻译，这些mrna参与了许多癌症和各种疾病的发病机制。基于近20年的工作，HuR现在被认为是一种治疗靶点。在此，我们将回顾HuR在不同疾病的病理生理中的作用以及目前针对HuR的治疗策略。我们将重点关注三个持续的靶向策略：(1)抑制HuR从细胞核向细胞质的易位；(2)抑制HuR结合靶RNA的能力；(3)抑制HuR表达水平。在肿瘤学环境中，HuR已被证明对癌细胞在各种癌症相关压力源（包括药物和肿瘤微环境元素）中存活的能力至关重要，并且靶向该蛋白已被证明可使癌细胞进一步对侮辱敏感。我们坚信，在不久的将来，靶向HuR可能成为治疗不同疾病，特别是癌症的强大治疗靶点。本文分类为：RNA在疾病和发展中的作用b> RNA在疾病中NRA的周转和监测> RNA稳定性翻译调控>翻译调控
Altered gene expression is a characteristic feature of many disease states such as tumorigenesis, and in most cancers, it facilitates cancer cell survival and adaptation. Alterations in global gene expression are strongly impacted by post-transcriptional gene regulation. The RNA binding protein (RBP) HuR (ELAVL1) is an established regulator of post-transcriptional gene regulation and is overexpressed in most human cancers. In many cancerous settings, HuR is not only overexpressed, but it is "overactive" as denoted by increased subcellular localization within the cytoplasm. This dysregulation of HuR expression and cytoplasmic localization allows HuR to stabilize and increase the translation of various prosurvival messenger RNA (mRNAs) involved in the pathogenesis of numerous cancers and various diseases. Based on almost 20 years of work, HuR is now recognized as a therapeutic target. Herein, we will review the role HuR plays in the pathophysiology of different diseases and ongoing therapeutic strategies to target HuR. We will focus on three ongoing-targeted strategies: (1) inhibiting HuR's translocation from the nucleus to the cytoplasm; (2) inhibiting the ability of HuR to bind target RNA; and (3) silencing HuR expression levels. In an oncologic setting, HuR has been demonstrated to be critical for a cancer cell's ability to survive a variety of cancer relevant stressors (including drugs and elements of the tumor microenvironment) and targeting this protein has been shown to sensitize cancer cells further to insult. We strongly believe that targeting HuR could be a powerful therapeutic target to treat different diseases, particularly cancer, in the near future. This article is categorized under: RNA in Disease and Development > RNA in Disease NRA Turnover and Surveillance > Regulation of RNA Stability Translation > Translation Regulation