Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Genetics, Tabriz, Iran.
Department of Vascular and Endovascular Surgery, Ayatollah Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Pathol Res Pract. 2023 Sep;249:154702. doi: 10.1016/j.prp.2023.154702. Epub 2023 Jul 20.
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.
乳腺癌（BC）的形成主要受遗传、表观遗传和环境因素的影响。异常的遗传学和表观遗传学导致了异质性的出现。BC 的异质性可以分为几个亚型。在表观遗传因素中，microRNAs（miRNAs）已被证明在恶性肿瘤的发生和发展中起着关键作用。这些小的非编码 RNA 通过多种机制调节基因表达，导致 mRNA 降解或翻译抑制。由于 miRNA 直接控制许多蛋白质，遗传异常会影响肿瘤转移、凋亡、增殖和细胞运输。因此，miRNA 的失调不仅参与了癌症的发展，还参与了侵袭性、增殖率，更重要的是，药物反应。研究结果大多表明，BC 中存在特定亚型的相同 miRNA 谱。在 BC 的亚型中，TNBC、HER2+和 luminal 分别是对治疗最具抵抗力的。治疗耐药性与 miRNA 表达谱密切相关。因此，miRNA 的浓度是其在化疗反应中的作用的第一个标志物。过表达的 miRNA 可能会破坏药物外排转运体并减少细胞内药物的积累。而下调 miRNA 介导的耐药过程与治疗反应不佳密切相关。此外，miRNA 在化疗耐药中的其他作用机制，如细胞受体介导、环境因素的失调、DNA 缺陷等，也发挥着至关重要的作用。最近，几种基于 miRNA 的治疗方法在癌症治疗中显示出了有希望的结果。抑制上调的 miRNA 是这些治疗方法之一，而转染下调的 miRNA 也显示出了有希望的结果。此外，还可以通过 miRNA 的表达水平在治疗前阶段来确定耐药性。因此，miRNA 为克服化疗耐药性提供了有趣的见解和挑战。在本文中，我们讨论了 miRNA 如何调节乳腺癌亚型特异性的化疗耐药性。
