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HuR-targeted agents: An insight into medicinal chemistry, biophysical, computational studies and pharmacological
Giulia Assoni1, Valeria La Pietra2, Rosangela Digilio3
1Chemistry 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.
Abstract:
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).
Insights
The Human antigen R (HuR) protein regulates RNA processing and is a key target in cancer therapy. Inhibiting HuR-mRNA interactions shows promise for treating cancer and inflammation.
Area of Science:
- Molecular Biology
- RNA Biology
- Oncology
Background:
- Human antigen R (HuR) is a ubiquitous RNA-binding protein involved in RNA maturation and processing.
- HuR plays critical roles in both normal cellular functions and disease states, including cancer and inflammation.
Purpose of the Study:
- To review the structure, mechanism, and modulators of HuR.
- To highlight HuR as a validated molecular target in oncology.
- To discuss the role of HuR in inflammation.
Main Methods:
- Literature review of HuR modulators, structure, and mechanism.
- Analysis of in vitro and in vivo studies on HuR's role in cancer.
- Examination of evidence for inhibiting HuR-mRNA interactions.
Main Results:
- HuR's structure includes RRM domains and it interacts with RNA, dimerizes, and binds inhibitors.
- HuR is implicated in the hallmarks of cancer.
- Inhibition of HuR-mRNA interactions via silencing or small molecules demonstrates anti-cancer effects.
Conclusions:
- HuR is a significant molecular target in oncology.
- Inhibiting HuR-mRNA interactions offers a therapeutic strategy for cancer treatment.
- HuR also plays a role in inflammatory processes.
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