Breast cancer remains the most prevalent malignancy and a leading cause of cancer-related mortality among women worldwide. Among its subtypes, triple-negative breast cancer (TNBC) is the most aggressive, characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Due to its heterogeneity and lack of targeted therapies, TNBC is associated with poor prognosis and high recurrence rates. Recent research has highlighted microRNAs (miRNAs) as regulators of TNBC progression and development by targeting key genes and modulating signaling pathways involved in tumor growth, metastasis, and treatment resistance [1, 2].
This study aims to provide insights into the role of miRNAs and their target genes in assessing cancer cell resistance to chemotherapy. Bioinformatic case study analysis of the cancer genome atlas (TCGA) datasets revealed 195 differentially expressed miRNAs targeting 57 genes linked to the platinum drug resistance pathway. Analysis of patient survival data showed 13 of those to be directly related to patient survival rate.
Based on these findings, we focused on selected miRNA expression levels in TNBC patient blood samples before and after neoadjuvant chemotherapy and their association with disease or residual cancer burden (RCB). We discovered that miR-340-5p expression is higher in the healthy control group compared to cancer patient samples before and after treatment. A notable increase in miR-340-5p expression levels was noted in the RCB-0-I group, comparing patient samples before and after chemotherapy, with levels rising post-chemotherapy. For miR-22-3p, expression levels were lower in patient samples compared to controls, and expression increased after chemotherapy in both RCB patient groups. These results underscore the potential tumor-suppressive roles of miR-340-5p and miR-22-3p. Additionally, we analyzed changes in the expression of target genes of these miRNAs in blood samples. Specifically, we focused on the expression of the miR-340-5p target genes DNMT3A, RHOA, and IGF1R, with IGF1R being a common target of both miR-340-5p and miR-22-3p. Furthermore, we performed KEGG pathway enrichment analysis to identify the signaling pathways influenced by these miRNA-regulated genes.
Gaining insights into the network of miRNA-target interactions and their role in TNBC-associated pathways offers new opportunities for therapeutic interventions and potential use as biomarkers for TNBC prognosis and treatment response.