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

Assoni, Giulia; Pietra, Valeria La; Digilio, Rosangela; Ciani, Caterina; Licata, Nausicaa Valentina; Micaelli, Mariachiara; Facen, Elisa; Tomaszewska, Weronika; Cerofolini, Linda; Pérez-Ràfols, Anna; Varela‐Rey, Marta; Fragai, Marco; Marinelli, Luciana; Bonomo, Isabelle; Provenzani, Alessandro; Seneci, Pierfausto

doi:10.1016/j.addr.2021.114088

Cited by 15 publications

(19 citation statements)

References 214 publications

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“…HuR is a potential therapeutic target candidate-related autophagy for disease therapy [27][28][29]. However, inhibiting HuR may cause many side effects because of the central functions of HuR, such as controlling mRNA stability and the expression of various cytokines, proto-oncogenes, and growth factors.…”

Section: Discussionmentioning

confidence: 99%

hucMSC treatment ameliorated pulmonary fibrosis via downregulating the circFOXP1–HuR–EZH2/STAT1/FOXK1 autophagic axis

Zhang

et al. 2022

Preprint

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Background Currently, no effective treatment has been developed for pulmonary fibrosis. This study was performed to determine the effect of human umbilical cord mesenchymal stem cell (hucMSC) treatment on pulmonary fibrosis and investigate the circFOXP1-mediated mechanism of hucMSC treatment on autophagy. Methods Pulmonary fibrosis models were established by spraying bleomycin in mice and TGF-β1 treatment of MRC-5 cell. The effect of hucMSC treatment was investigated using morphological and functional experiments. The mechanism of hucMSC treatment in pulmonary fibrosis was explored by gain- and loss-of-function studies and rescue experiments. Results Results showed that hucMSC treatment alleviated pulmonary fibrosis. Morphological staining indicated that hucMSC-treated mice had thinner alveolar wall, effectively improved alveolar structure, significantly reduced alveolar inflammation, and decreased collagen deposition than control mice. Fibrotic proteins, including vimentin, α-SMA, collagen I, and collagen III, and the differentiation-related protein S100 calcium binding protein A4 were reduced considerably in the hucMSC-treated group. The mechanistic study revealed that the inhibition of hucMSC treatment on pulmonary fibrogenesis depended on downregulating circFOXP1, in which hucMSC treatment promoted circFOXP1-mediated autophagy process via blocking the nuclear HuR translocation and promoting the HuR degradation, leading to a marked decrease in autophagy negative regulators EZH2, STAT1 and FOXK1. Conclusion hucMSC treatment significantly improved pulmonary fibrosis by downregulating the circFOXP1–HuR–EZH2/STAT1/FOXK1 autophagic axis. hucMSCs can act as an effective treatment for pulmonary fibrosis.

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Section: Discussionmentioning

confidence: 99%

hucMSC treatment ameliorated pulmonary fibrosis via downregulating the circFOXP1–HuR–EZH2/STAT1/FOXK1 autophagic axis

Zhang

et al. 2022

Preprint

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“…Recombinant AB-Elavl (rAB-Elavl) protein encoded in plasmid pET-30a(+) was overexpressed in BL21(DE3) GOLD cells. Cells were grown in LB or M9 minimal media supplemented with 15 NH 4 Cl or 15 NH 4 Cl and 13 C-glucose at 37 • C until optical density (OD 600 ) reached 0.6-0.8. Subsequently, protein production was induced with 0.2 mM of isopropyl β-D-thiogalactoside (IPTG), cells were incubated at 18 • C overnight and harvested by centrifugation at 4 • C, for 15 min at 7500 rpm.…”

Section: Expression and Purification Of Rab-elavl For X-ray And Nmr A...mentioning

confidence: 99%

“…Experiments for backbone assignment were performed on samples of the 13 C, 15 N isotopically enriched RRM domain of rAB-Elavl at protein concentration of 300 µM in buffer solution (20 mM HEPES, pH 6.8, 150 mM NaCl, 3 mM MgCl 2 , Proteases Inhibitor Cocktail). NMR spectra were recorded at 298 K on a Bruker AVANCE NEO 900 spectrometer, equipped with a triple-resonance Cryo-Probe (Bruker, Billerica, MA, USA).…”

Section: Nmr Measurements and Protein Assignmentmentioning

confidence: 99%

“…The effect of two different types of RNA (AREpos and AREneg) on the 15 N-isotopically enriched RRM domain of AB-Elavl (70 µM) was evaluated in the following experimental conditions: 20 mM HEPES, pH 6.8, 150 mM NaCl, 3 mM MgCl 2 , Proteases Inhibitor Cocktail. 2D 1 H 15 N BEST-TROSY.…”

Section: Titration Of Rab-elavl With Rna Probesmentioning

confidence: 99%

“…ELAV-Like proteins bind specific sequences of RNA called AU-Rich Elements (ARE) characterized by the enriched presence of adenylates and uridylates. AREs can be located either in the intronic regions as well as in coding or non-coding parts of the mature mRNA, and contribute to mRNA splicing, maturation, stabilization, and translation [ 5 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Identification and Characterization of an RRM-Containing, RNA Binding Protein in Acinetobacter baumannii

et al. 2022

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Acinetobacter baumannii is a Gram-negative pathogen, known to acquire resistance to antibiotics used in the clinic. The RNA-binding proteome of this bacterium is poorly characterized, in particular for what concerns the proteins containing RNA Recognition Motif (RRM). Here, we browsed the A. baumannii proteome for homologous proteins to the human HuR(ELAVL1), an RNA binding protein containing three RRMs. We identified a unique locus that we called AB-Elavl, coding for a protein with a single RRM with an average of 34% identity to the first HuR RRM. We also widen the research to the genomes of all the bacteria, finding 227 entries in 12 bacterial phyla. Notably we observed a partial evolutionary divergence between the RNP1 and RNP2 conserved regions present in the prokaryotes in comparison to the metazoan consensus sequence. We checked the expression at the transcript and protein level, cloned the gene and expressed the recombinant protein. The X-Ray and NMR structural characterization of the recombinant AB-Elavl revealed that the protein maintained the typical β1α1β2β3α2β4 and three-dimensional organization of eukaryotic RRMs. The biochemical analyses showed that, although the RNP1 and RNP2 show differences, it can bind to AU-rich regions like the human HuR, but with less specificity and lower affinity. Therefore, we identified an RRM-containing RNA-binding protein actually expressed in A. baumannii.

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RNA binding proteins (RBPs) and their role in DNA damage and radiation response in cancer

Mehta

Raguraman

Ramesh

et al. 2022

Advanced Drug Delivery Reviews

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

Cited by 15 publications

References 214 publications

hucMSC treatment ameliorated pulmonary fibrosis via downregulating the circFOXP1–HuR–EZH2/STAT1/FOXK1 autophagic axis

hucMSC treatment ameliorated pulmonary fibrosis via downregulating the circFOXP1–HuR–EZH2/STAT1/FOXK1 autophagic axis

Identification and Characterization of an RRM-Containing, RNA Binding Protein in Acinetobacter baumannii

RNA binding proteins (RBPs) and their role in DNA damage and radiation response in cancer

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