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.

中文翻译：

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了解并靶向与疾病相关的RNA结合蛋白人类抗原R（HuR）。

基因表达的改变是许多疾病状态的特征，例如肿瘤发生，并且在大多数癌症中，它促进癌细胞的存活和适应。转录后基因调控强烈影响全局基因表达的变化。RNA结合蛋白（RBP）HuR（ELAVL1）是转录后基因调控的公认调控因子，在大多数人类癌症中均过表达。在许多癌性环境中，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。HuR表达和细胞质定位的这种失调使HuR能够稳定并增加参与多种癌症和各种疾病发病机理的各种生存信使RNA（mRNA）的翻译。基于将近20年的工作，HuR现在被认为是治疗靶标。在此，我们将回顾HuR在不同疾病的病理生理中所起的作用以及针对HuR的现行治疗策略。我们将着眼于三种正在进行的靶向策略：（1）抑制HuR从细胞核到细胞质的转运；（2）抑制HuR结合靶RNA的能力；（3）沉默HuR表达水平。在肿瘤学背景下，已证明HuR对于癌细胞在各种与癌症相关的应激源（包括药物和肿瘤微环境的成分）中生存的能力至关重要，并且已证明靶向该蛋白可使癌细胞进一步敏感。我们坚信，靶向HuR可能是在不久的将来治疗各种疾病（尤其是癌症）的强大治疗靶标。