The impact of microRNAs on the resistance of breast cancer subtypes to chemotherapy

Abstract

Breast cancer (BC) formation is primarily influenced by genetics, epigenetics and environmental factors. Aberrant Genetics and epigenetics leads to a condition known as heterogeneity. The heterogeneity of BC can be divided into several subtypes. Among the epigenetic factors, microRNAs (miRNAs) have been shown to play a crucial role in the development and progression of malignancies. These small non-coding RNAs regulate gene expression through a variety of mechanisms, resulting in either mRNA degradation or translation repression. As miRNAs directly control many proteins, genetic anomalies affect tumor metastasis, apoptosis, proliferation, and cell transportation. Consequently, miRNA dysregulations contribute not only in cancer development but also in invasiveness, proliferation rate and more importantly, drug response. Findings mostly indicate subtype-specified identical miRNA profile in BC. Among the BC subtypes, TNBC, HER2 + and luminal are the most resistant to therapy, respectively. Therapy resistance is greatly associated with miRNA expression profile. Hence, concentration of miRNA is the first marker of its role in chemotherapy response. Overexpressed miRNAs may disrupt drug efflux transporters and decrease the drug accumulation in cell. While down-regulated miRNAs which mediate drug resistance processes are mostly correlated with poor treatment response. Moreover, other mechanisms in which miRNAs play crucial roles in chemoresistance such as cell receptor mediations, dysregulation by environmental factors, DNA defects, etc. Recently, several miRNA-based treatments have shown promising results in cancer treatment. Inhibition of up-regulated miRNAs is one of these therapeutic approaches whilst transfecting cell with down-regulated miRNAs also show promising results. Moreover, drug-resistance could also be determined while in the pre-treatment phase via expression levels of miRNAs. Therefore, miRNAs provide intriguing insights and challenges in overcoming chemoresistance. In this article, we have discussed how miRNAs regulate breast cancer subtypes-specific chemoresistance.

Keywords: Breast Cancer; Chemoresistance; MicroRNA; Subtype.