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Updated: Jul 26, 2025
Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization
Published on: June 7, 2016
An integrated analysis of microRNAs regulating DNA damage response in triple-negative breast cancer
Raviprasad Kuthethur1, Maria Sona Jerome1, Yashwanth Subbannayya2,3
1Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
Background:
Triple-negative breast cancer (TNBC) remains a clinical challenge due to its aggressive phenotype and limited treatment options for the patients. Many TNBC patients show an inherent defect in the DNA repair capacity primarily by acquiring germline mutations in BRCA1 and BRCA2 genes leading to Homologous Recombination Deficiency (HRD). Epigenetic modifications such as BRCA1 promoter methylation and miRNA expression targeting DNA repair pathway genes have contributed to the HRD phenotype in TNBC. Hence, we aimed to identify microRNAs that are associated with HRD status in the TCGA-BRCA project.
Materials And Methods:
We implemented a miRNA prediction strategy for identifying miRNAs targeting HR pathway genes using an in silico predicted and experimentally validated list from published literature for their association with genomic instability and factors affecting HRD. In silico analysis was performed to study miRNA expression patterns regulated by DNA methylation and TMB status in the TNBC patients from TCGA-BRCA project. Finally, we analysed selected miRNA expression with immune cell infiltration pattern in the TNBC patient cohort.
Results:
Our study identified miRNAs associated with HRD, tumour mutation burden (TMB), and immune cell infiltration. Identified miRNA signatures were associated with the miR-17 ~ 92 cluster, miR-106b ~ 25 cluster, and miR-200b ~ 429 cluster. Pathway analysis of selected miRNAs suggested their association with altered immune cell infiltration in TNBC.
Conclusion:
Our study identified 6 'HRD associated miRNAs' such as miR-106b, miR-93, miR-17, miR-20a, miR-200b, and miR-429 as novel miRNA-based signatures associated with HR deficiency in TNBC.
Insights
This study identifies six microRNAs (miRNAs) linked to homologous recombination deficiency (HRD) in triple-negative breast cancer (TNBC). These HRD-associated miRNAs may serve as novel biomarkers for TNBC patients.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its aggressive nature and limited therapeutic strategies.
- Homologous Recombination Deficiency (HRD), often caused by BRCA1/2 mutations, is prevalent in TNBC and impacts DNA repair capacity.
- Epigenetic factors, including BRCA1 promoter methylation and microRNA (miRNA) dysregulation, contribute to HRD in TNBC.
Purpose of the Study:
- To identify specific microRNAs associated with HRD status in triple-negative breast cancer.
- To explore the relationship between miRNA expression, tumor mutation burden (TMB), and immune cell infiltration in TNBC.
- To discover novel miRNA-based signatures for HRD in TNBC patients.
Main Methods:
- A miRNA prediction strategy was employed, integrating in silico analysis and published literature to identify miRNAs targeting HR pathway genes.
- In silico analysis examined miRNA expression patterns in relation to DNA methylation and TMB status within the TCGA-BRCA project cohort.
- The expression of selected miRNAs was analyzed in conjunction with immune cell infiltration patterns in TNBC patients.
Main Results:
- The study identified several microRNAs associated with HRD, tumor mutation burden (TMB), and immune cell infiltration in TNBC.
- Key miRNA signatures identified were linked to the miR-17~92 cluster, miR-106b~25 cluster, and miR-200b~429 cluster.
- Pathway analysis indicated that the selected miRNAs are associated with altered immune cell infiltration in TNBC.
Conclusions:
- Six 'HRD associated miRNAs' were identified: miR-106b, miR-93, miR-17, miR-20a, miR-200b, and miR-429.
- These miRNAs represent novel, miRNA-based signatures associated with HR deficiency in triple-negative breast cancer.
- The findings suggest potential utility of these miRNAs as biomarkers for HRD in TNBC.
