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JARID1B expression and its function in DNA damage repair are tightly regulated by miRNAs in breast cancer
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 e...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447846/ https://www.ncbi.nlm.nih.gov/pubmed/30588710 http://dx.doi.org/10.1111/cas.13925 |
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author | Mocavini, Ivano Pippa, Simone Licursi, Valerio Paci, Paola Trisciuoglio, Daniela Mannironi, Cecilia Presutti, Carlo Negri, Rodolfo |
author_facet | Mocavini, Ivano Pippa, Simone Licursi, Valerio Paci, Paola Trisciuoglio, Daniela Mannironi, Cecilia Presutti, Carlo Negri, Rodolfo |
author_sort | Mocavini, Ivano |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6447846 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64478462019-04-15 JARID1B expression and its function in DNA damage repair are tightly regulated by miRNAs in breast cancer Mocavini, Ivano Pippa, Simone Licursi, Valerio Paci, Paola Trisciuoglio, Daniela Mannironi, Cecilia Presutti, Carlo Negri, Rodolfo Cancer Sci Original Articles 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. John Wiley and Sons Inc. 2019-03-18 2019-04 /pmc/articles/PMC6447846/ /pubmed/30588710 http://dx.doi.org/10.1111/cas.13925 Text en © 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 http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Mocavini, Ivano Pippa, Simone Licursi, Valerio Paci, Paola Trisciuoglio, Daniela Mannironi, Cecilia Presutti, Carlo Negri, Rodolfo JARID1B expression and its function in DNA damage repair are tightly regulated by miRNAs in breast cancer |
title |
JARID1B expression and its function in DNA damage repair are tightly regulated by miRNAs in breast cancer |
title_full |
JARID1B expression and its function in DNA damage repair are tightly regulated by miRNAs in breast cancer |
title_fullStr |
JARID1B expression and its function in DNA damage repair are tightly regulated by miRNAs in breast cancer |
title_full_unstemmed |
JARID1B expression and its function in DNA damage repair are tightly regulated by miRNAs in breast cancer |
title_short |
JARID1B expression and its function in DNA damage repair are tightly regulated by miRNAs in breast cancer |
title_sort | jarid1b expression and its function in dna damage repair are tightly regulated by mirnas in breast cancer |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447846/ https://www.ncbi.nlm.nih.gov/pubmed/30588710 http://dx.doi.org/10.1111/cas.13925 |
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