Investigation of BRCAness associated miRNA-gene axes in breast cancer: cell-free miR-182-5p as a potential expression signature of BRCAness.

Abstract

The concept of the 'BRCAness' phenotype implies the properties that some sporadic breast cancers (BC) share with BRCA1/2-mutation carriers with hereditary BC. Breast tumors with BRCAness have deficiencies in homologous recombination repair (HRR), like BRCA1/2-mutation carriers, and consequently could benefit from poly-(ADP)-ribose polymerase (PARP) inhibitors and DNA-damaging chemotherapy. Triple-negative breast cancers (TNBC) show a higher frequency of BRCAness than the other BC subtypes. Therefore, looking for BRCAness-related biomarkers could improve personalized management of TNBC patients. microRNAs (miRNAs) play a pivotal role in onco-transcriptomic profiles of tumor cells besides their suitable features as molecular biomarkers. The current study aims to evaluate the expression level of some critical miRNAs-mRNA axes in HRR pathway in tumors and plasma samples from BC patients. The expression levels of three multi-target miRNAs, including miR-182-5p, miR-146a-5p, and miR-498, as well as six downstream HRR-related protein-coding genes, have been investigated in the breast tumors and paired adjacent normal tissues by Real-time PCR. In the next step, based on the results derived from the previous step, we examined the level of cell-free miR-182-5p in the blood plasma samples from the patients. Our results highlight the difference between TNBC and non-TNBC tumor subgroups regarding the dysregulation of the key miRNA/mRNA axes involved in the HRR pathway. Also, for the first time, we show that the level of cell-free miR-182-5p in plasma samples from BC patients could be a clue for screening BC patients eligible for receiving PARP inhibitors through a personalized manner. Altogether, some sporadic BC patients, especially sporadic TNBC, have epigenetically dysregulated HRR pathway that could be identified and benefit from BRCAness-specific therapeutic agents.

• Authors: Farzaneh Darbeheshti, Sepideh Kadkhoda, Mahsa Keshavarz-Fathi, Sepideh Razi, Afshin Bahramy, Yaser Mansoori, Nima Rezaei
• Journal: BMC cancer (BMC Cancer) Vol. 22 Issue 1 Pg. 668 (Jun 17 2022) ISSN: 1471-2407 [Electronic] England
• PMID: 35715772 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• BRCA1 Protein
• BRCA1 protein, human
• BRCA2 Protein
• BRCA2 protein, human
• MIRN498 microRNA, human
• MicroRNAs
• Mirn182 microRNA, human
• Poly(ADP-ribose) Polymerase Inhibitors
• RNA, Messenger
• Poly(ADP-ribose) Polymerases

Topics

• BRCA1 Protein (biosynthesis, genetics)
• BRCA2 Protein (biosynthesis, genetics)
• Humans
• MicroRNAs (genetics, metabolism)
• Poly(ADP-ribose) Polymerase Inhibitors (pharmacology)
• Poly(ADP-ribose) Polymerases (metabolism)
• RNA, Messenger (genetics, metabolism)
• Triple Negative Breast Neoplasms (drug therapy, genetics, metabolism, pathology)