Introduction: 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.
Methods: Methods and Materials: We searched for existing articles in PubMed, Web of Science, Cochrane, Scopus, and RNA central databases up to april 2023. A total of 102 articles were qualified and included in the present review. .In this review, we intend to assess the influence of miRNAs on chemoresistance in subtypes of BC as the main epigenetic factors. Expression, targeted genes and consequently regulated processes are the features that are evaluated. and included.
Results: Due to response differences, subtype identification is obligatory before drug prescription for BC. These drugs mostly modulate hormonal status, drug transportation and efflux and some vital processes like cell junction. Alongside the genes, miRNAs show promising findings in chemoresistance and chemotherapy . We have observed down regulation of some miRNAs such as mir-143–3p, mir-512–3p, mir326 and mir-451a cause weak drug-response whereas, up-regulation of some miRNAs such as mir-135b-5p, mir-221, mir-186–5p and mir-21–5p may originate the same problem. Recognizing processes mediated by these miRNAs provide helpful insights and suggest practical therapeutic targets. Moreover, metastasis, adhesion, signaling pathways, cell proliferation, DNA damage repair and cell transport system are among the most important functions regulated by miRNAs. In addition, identification of differentially expressed miRNAs in chemoresistance tissue is highly precious as they provide valuable diagnostic biomarkers . MiRNAs can also be informative about prognosis of the cancer. In case of treatment, adjusting cell miRNA expression level, targeted gene therapy, TME modifying and designing combined treatment based on miRNA-Drug combination are the most commonly accepted approaches. Also, new therapeutic methods are carried out using miRNAs as drug-enhancers.
Conclusion: Collectively, we have briefly elaborated the influences of miRNAs in chemoresistance, potential applications, therapeutic approaches and miRNA expression aberrancies in BC subtypes. This study may be beneficial in processing further miRNA based treatments
Keywords: MicroRNA, Breast Cancer Subtype, Chemoresistance