Chemistry Department, University of Milan, Via Golgi 19, I-20133 Milan, Italy; Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, via Sommarive 9, 38123 Trento, Italy.
Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Adv Drug Deliv Rev. 2022 Feb;181:114088. doi: 10.1016/j.addr.2021.114088. Epub 2021 Dec 20.
The Human antigen R (HuR) protein is an RNA-binding protein, ubiquitously expressed in human tissues, that orchestrates target RNA maturation and processing both in the nucleus and in the cytoplasm. A survey of known modulators of the RNA-HuR interactions is followed by a description of its structure and molecular mechanism of action - RRM domains, interactions with RNA, dimerization, binding modes with naturally occurring and synthetic HuR inhibitors. Then, the review focuses on HuR as a validated molecular target in oncology and briefly describes its role in inflammation. Namely, we show ample evidence for the involvement of HuR in the hallmarks and enabling characteristics of cancer, reporting findings from in vitro and in vivo studies; and we provide abundant experimental proofs of a beneficial role for the inhibition of HuR-mRNA interactions through silencing (CRISPR, siRNA) or pharmacological inhibition (small molecule HuR inhibitors).
人抗原 R（HuR）蛋白是一种 RNA 结合蛋白，在人类组织中广泛表达，可协调靶 RNA 在核内和细胞质中的成熟和加工。对已知的 RNA-HuR 相互作用调节剂进行调查后，本文描述了其结构和分子作用机制——RRM 结构域、与 RNA 的相互作用、二聚化、与天然和合成 HuR 抑制剂的结合模式。然后，综述重点关注 HuR 作为肿瘤学中经过验证的分子靶点，并简要描述其在炎症中的作用。具体来说，我们提供了大量证据表明 HuR 参与了癌症的标志和实现特征，报告了来自体外和体内研究的发现；并通过沉默（CRISPR、siRNA）或药理学抑制（小分子 HuR 抑制剂）提供了大量实验证据，证明抑制 HuR-mRNA 相互作用具有有益作用。
