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Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization
06:01

Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization

Published on: June 7, 2016

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

Ivano Mocavini1, Simone Pippa2, Valerio Licursi3

  • 1Centre for Genomic Regulation, Barcelona, Spain.

Cancer Science
|December 28, 2018
PubMed

Insights

JARID1B/KDM5B histone demethylase is overexpressed in breast cancer. Two microRNAs (miRNAs), mir-381 and mir-486, were found to target JARID1B mRNA, potentially offering new epigenetic therapy strategies.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • JARID1B/KDM5B histone demethylase mRNA is overexpressed in breast cancer.
  • JARID1B plays a role in cancer cell proliferation and DNA repair.
  • The post-transcriptional regulation of JARID1B in cancer remains unclear.

Purpose of the Study:

  • To investigate the post-transcriptional regulation of JARID1B in breast cancer.
  • To identify microRNAs (miRNAs) that target JARID1B mRNA.
  • To explore the therapeutic potential of miRNA-mediated JARID1B regulation.

Main Methods:

  • Computational analysis of transcriptomic data from 103 breast cancer patients.
  • Luciferase reporter assays to confirm miRNA targeting of JARID1B 3'UTR.
  • Transfection of MCF7 breast cancer cells with mir-486 to assess JARID1B protein levels and cellular effects.

Main Results:

  • JARID1B upregulation correlated with downregulation of mir-381 and mir-486.
  • Both miRNAs directly target JARID1B mRNA's 3'UTR.
  • Mir-486 transfection reduced JARID1B protein, induced DNA damage, enhanced radiosensitivity, and increased BRCA1 mRNA.

Conclusions:

  • A miRNA circuit involving mir-381 and mir-486 regulates JARID1B activity in breast cancer.
  • This miRNA-JARID1B interaction presents potential new avenues for epigenetic therapies.
  • Targeting this pathway could offer novel treatment strategies for breast cancer.
Keywords:
DNA damageIonizing radiationKDM5 histone demethylasebreast cancermicroRNA

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