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JARID1B expression and its function in DNA damage repair are tightly regulated by miRNAs in breast cancer

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dc.contributor.author Mocavini, Ivano
dc.contributor.author Pippa, Simone
dc.contributor.author Licursi, Valerio
dc.contributor.author Paci, Paola
dc.contributor.author Trisciuoglio, Daniela
dc.contributor.author Mannironi, Cecilia
dc.contributor.author Presutti, Carlo
dc.contributor.author Negri, Rodolfo
dc.date.accessioned 2019-07-16T09:27:15Z
dc.date.available 2019-07-16T09:27:15Z
dc.date.issued 2019
dc.identifier.citation Mocavini I, Pippa S, Licursi V, Paci P, Trisciuoglio D, Mannironi C et al. JARID1B expression and its function in DNA damage repair are tightly regulated by miRNAs in breast cancer. Cancer Sci. 2019 Apr;110(4):1232-43. DOI: 10.1111/cas.13925
dc.identifier.issn 1347-9032
dc.identifier.uri http://hdl.handle.net/10230/42002
dc.description.abstract JARID1B/KDM5B histone demethylase's mRNA is markedly overexpressed in breast cancer tissues and cell lines and the protein has been shown to have a prominent role in cancer cell proliferation and DNA repair. However, the mechanism of its post-transcriptional regulation in cancer cells remains elusive. We performed a computational analysis of transcriptomic data from a set of 103 breast cancer patients, which, along with JARID1B upregulation, showed a strong downregulation of 2 microRNAs (miRNAs), mir-381 and mir-486, potentially targeting its mRNA. We showed that both miRNAs can target JARID1B 3'UTR and reduce luciferase's activity in a complementarity-driven repression assay. Moreover, MCF7 breast cancer cells overexpressing JARID1B showed a strong protein reduction when transfected with mir-486. This protein's decrease is accompanied by accumulation of DNA damage, enhanced radiosensitivity and increase of BRCA1 mRNA, 3 features previously correlated with JARID1B silencing. These results enlighten an important role of a miRNA's circuit in regulating JARID1B's activity and suggest new perspectives for epigenetic therapies.
dc.description.sponsorship Funding information: Sapienza Research Grant. Grant Number: RM11715C53A3F678
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Wiley Open Access
dc.relation.ispartof Cancer Science. 2019 Apr;110(4):1232-43
dc.rights © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes
dc.rights.uri https://creativecommons.org/licenses/by-nc/4.0/
dc.subject.other Mama -- Càncer
dc.subject.other ADN -- Dany
dc.subject.other ADN -- Reparació
dc.subject.other Expressió gènica
dc.subject.other Oxidoreductases
dc.subject.other Genètica
dc.title JARID1B expression and its function in DNA damage repair are tightly regulated by miRNAs in breast cancer
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1111/cas.13925
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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