Insights into multidrug resistance mechanisms: Exploring distinct miRNAs as prospective therapeutic agents in triple negative breast cancer

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2024-09-03 DOI:10.1016/j.genrep.2024.102020

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引用次数: 0

Abstract

Triple Negative Breast Cancer (TNBC) constitutes 12–17 % of breast cancers and is distinguished by the absence of hormone receptor expression, deviating from other breast cancer types. Coupled with its elevated proliferation index, TNBC develops multidrug resistance, diminishing treatment efficacy, weakening disease prognosis, and leading to an aggressive clinical course. This study aimed to assess ABCB1, ABCC1, ABCG2, and ABCC9 gene expression, which play a primary role in the development of multidrug resistance, alongside miRNAs (miR-466, miR-4539, miR-659-3p, miR-3123, miR-3133, and miR-655-3p) targeting these genes. While ABCB1 (p = 0.433), ABCC1 (p < 0.05), and ABCG2 (p < 0.05) exhibited increased expression in tumor tissues, ABCC9 (p = 0.587) did not. miR-466 (p = 0.802), miR-4539 (p = 0.732), miR-659-3p (p = 0.807), and miR-3123 (p = 0.980) were upregulated, whereas miR-3133 (p < 0.05) and miR-655-3p (p = 0.190) were downregulated. Within the scope of our study, we also evaluated the clinical parameters like tumor size, stage, and neoadjuvant treatment that significantly impacted Progression Free Survival (PFS) and Overall Survival (OS). Considering these results, we found that the metastatic status significantly influenced PFS and OS. Chemotherapeutics were found to not affect survival times. Assessing the impact of miRNAs, which we view as potential therapeutic targets, on average survival revealed that elevated miR-3133 expression was correlated with shorter PFS and OS, whereas decreased miR-655-3p expression was associated with longer PFS and OS. In summary, the relevant miRNAs could serve as predictive biomarkers for drug response and aid in developing miRNA-targeted gene therapy strategies.

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洞察多药耐药性机制：探索作为三阴性乳腺癌前瞻性治疗药物的独特 miRNAs

三阴性乳腺癌（TNBC）占乳腺癌的 12-17%，其特点是没有激素受体表达，与其他乳腺癌类型不同。TNBC 的特点是没有激素受体表达，与其他乳腺癌类型不同，再加上其增殖指数升高，TNBC 会产生多药耐药性，从而降低治疗效果，削弱疾病预后，并导致侵袭性临床病程。本研究旨在评估在多药耐药性形成过程中起主要作用的ABCB1、ABCC1、ABCG2和ABCC9基因表达，以及靶向这些基因的miRNA（miR-466、miR-4539、miR-659-3p、miR-3123、miR-3133和miR-655-3p）。虽然 ABCB1（p = 0.433）、ABCC1（p < 0.05）和 ABCG2（p < 0.05）在肿瘤组织中的表达增加，但 ABCC9（p = 0.587）没有增加。802）、miR-4539（p = 0.732）、miR-659-3p（p = 0.807）和 miR-3123 （p = 0.980）上调，而 miR-3133 （p < 0.05）和 miR-655-3p （p = 0.190）下调。在研究范围内，我们还评估了对无进展生存期（PFS）和总生存期（OS）有显著影响的肿瘤大小、分期和新辅助治疗等临床参数。考虑到这些结果，我们发现转移状态对无进展生存期和总生存期有明显影响。化疗对生存时间没有影响。在评估被我们视为潜在治疗靶点的miRNA对平均生存期的影响时发现，miR-3133表达的升高与较短的PFS和OS相关，而miR-655-3p表达的降低与较长的PFS和OS相关。总之，相关的 miRNA 可作为药物反应的预测性生物标志物，有助于开发 miRNA 靶向基因治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.