JARID1B expression and its function in DNA damage repair are tightly regulated by miRNAs in breast cancer.
Biomarkers, Tumor
Breast Neoplasms
/ genetics
Cell Cycle
/ genetics
Cell Line, Tumor
DNA Damage
DNA Repair
Epigenesis, Genetic
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genes, Reporter
Humans
Jumonji Domain-Containing Histone Demethylases
/ genetics
MicroRNAs
/ genetics
Nuclear Proteins
/ genetics
RNA Interference
Radiation Tolerance
/ genetics
Repressor Proteins
/ genetics
Reproducibility of Results
Transcriptome
DNA damage
Ionizing radiation
KDM5 histone demethylase
breast cancer
microRNA
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
03
05
2018
revised:
13
12
2018
accepted:
16
12
2018
pubmed:
28
12
2018
medline:
17
4
2019
entrez:
28
12
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30588710
doi: 10.1111/cas.13925
pmc: PMC6447846
doi:
Substances chimiques
Biomarkers, Tumor
0
MicroRNAs
0
Nuclear Proteins
0
Repressor Proteins
0
Jumonji Domain-Containing Histone Demethylases
EC 1.14.11.-
KDM5B protein, human
EC 1.14.11.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1232-1243Subventions
Organisme : Sapienza Research Grant
ID : RM11715C53A3F678
Informations de copyright
© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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