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).

HuR-targeted agents: An insight into medicinal chemistry, biophysical, computational studies and pharmacological effects on cancer models / G. Assoni, V. La Pietra, R. Digilio, C. Ciani, N.V. Licata, M. Micaelli, E. Facen, W. Tomaszewska, L. Cerofolini, A. Pérez-Ràfols, M. Varela Rey, M. Fragai, A. Woodhoo, L. Marinelli, D. Arosio, I. Bonomo, A. Provenzani, P. Seneci. - In: ADVANCED DRUG DELIVERY REVIEWS. - ISSN 0169-409X. - 181:(2022 Feb), pp. 114088.1-114088.27. [10.1016/j.addr.2021.114088]

HuR-targeted agents: An insight into medicinal chemistry, biophysical, computational studies and pharmacological effects on cancer models

P. Seneci
Ultimo
2022

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).
Chemical features of HuR modulators; Hallmarks of cancer; HuR modulators; HuR role in immunity; Structural interactions of HuR modulators; Animals; Drug Delivery Systems; ELAV-Like Protein 1; Gene Silencing; Humans; Inflammation Mediators; Molecular Weight; Neoplasms; RNA; RNA, Messenger; RNA, Small Interfering
Settore CHIM/06 - Chimica Organica
20-dic-2021
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/944071
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