Triple negative breast cancer: microRNA expression profile and novel discriminators according to BRCA1 status

J Cell Physiol. 2020 Jun;235(6):5204-5212. doi: 10.1002/jcp.29398. Epub 2019 Nov 17.

Abstract

Triple-negative breast cancer (TNBC) represents 15% of breast carcinomas. More than 80% of women with a breast cancer associated with a breast cancer type 1 (BRCA1) mutation develop a TNBC. microRNAs (miRNAs) play critical roles in diverse biological processes and are aberrantly expressed in several human neoplasms including breast cancer, where they function as actors of tumor onset, behavior, and progression. However, an extensive microRNA profile has not yet been determined for TNBC. Taqman low-density arrays (TLDAs) were used to screen the expression level of 667 miRNAs in TNBC versus normal breast tissues. Our TLDA results revealed 20 differentially expressed miRNAs among which 14 (10 upregulated and four downregulated) were confirmed by an individual quantitative real-time polymerase chain reaction. Interestingly, a novel link between BRCA1 status and miRNA expression level was identified through miR-96 and miR-10b that were very important discriminators between TNBC with mutated BRCA1 and TNBC with wild type BRCA1. This study promises discoveries of new pathological pathways at work in this dreadful disease and clearly warrants validation in large prospective studies with the aim of identifying novel biomarkers for diagnosis and targets for clinical interventions.

Keywords: BRCA1; TNBC; breast cancer; microRNA.

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics*
  • Biomarkers, Tumor / genetics*
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs / genetics*
  • Middle Aged
  • Mutation / genetics
  • Progression-Free Survival
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • Biomarkers, Tumor
  • MicroRNAs