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评估埃及女性乳腺癌相关的肿瘤生成 miRNA:回顾性、探索性分析。

Evaluation of tumorigenesis-related miRNAs in breast cancer in Egyptian women: a retrospective, exploratory analysis.

机构信息

Department of Microbial Biotechnology, Biotechnology Research Institute, National Research Centre, EL Bohouth St. (Former El Tahrir St.), Dokki, P.O. 12622, Giza, Egypt.

Medical Molecular Genetic Department, Human Genetics and Genome Research Institute, National Research Centre, P.O. 12622, Dokki, Giza, Egypt.

出版信息

Sci Rep. 2024 Nov 29;14(1):29757. doi: 10.1038/s41598-024-68758-0.

Abstract

Breast cancer (BC) is a leading cause of global female cancer-related deaths, despite treatment advancements. A growing focus on investigating microRNA-based therapeutics and their role in BC progression. A computational analysis was performed to identify the potential miRNA-mRNA network involved in the BC pathogenesis and assist with the treatment strategy. Then, the expression levels of five circulatory miRNAs (miR-200a-3p, miR-124-3p, miR-205-5p, miR-15a-5p, and miR-155-5p) were assessed by using qRT-PCR in 75 BC patients (early-stage: n = 26 and late-stage: n = 49) and 20 healthy controls. The analysis included various (a) stages (early and late) and (b) receptor statuses (ER + ve & HER2 -ve), (HER + ve & ER -ve), and triple-negative (TNBC). In-silico analysis suggested that STAT3 serves as an efficacy biomarker suppressed by miR-124-3p. Additionally, the miR-155-5p showed the ability to activate CTNNB1 which acts as a biomarker for BC progression, to inhibit DNA repair genes (ARID2, and WEE1), and the transcriptional factor gene (TCF4). MiR-205-5p and miR-16 suppressed VEGFA expression, a survival factor for BC. MiR-200a-3p, miR-205-5p, and miR-124-3p showed downregulation in the serum of BC patients compared to controls. The ROC analysis of those miRNAs demonstrated their significant diagnostic accuracy for identifying BC patients. Additionally, miR-155-5p exhibited a significant upregulation in TNBC and can be used as an indicative marker for TNBC. This study holds significant promise for the development of noninvasive miRNA biomarkers with potential clinical applications.

摘要

乳腺癌 (BC) 是全球女性癌症相关死亡的主要原因,尽管治疗有所进展。目前越来越关注基于 microRNA 的治疗方法及其在 BC 进展中的作用。进行了计算分析,以确定参与 BC 发病机制的潜在 miRNA-mRNA 网络,并协助制定治疗策略。然后,通过 qRT-PCR 在 75 名 BC 患者(早期:n=26,晚期:n=49)和 20 名健康对照者中评估了五种循环 miRNA(miR-200a-3p、miR-124-3p、miR-205-5p、miR-15a-5p 和 miR-155-5p)的表达水平。分析包括各种 (a) 阶段(早期和晚期)和 (b) 受体状态(ER+ve & HER2-ve)、(HER+ve & ER-ve) 和三阴性 (TNBC)。计算机分析表明,STAT3 是受 miR-124-3p 抑制的疗效生物标志物。此外,miR-155-5p 能够激活 CTNNB1,后者是 BC 进展的生物标志物,抑制 DNA 修复基因 (ARID2 和 WEE1) 和转录因子基因 (TCF4)。miR-205-5p 和 miR-16 抑制 VEGFA 的表达,后者是 BC 的生存因子。miR-200a-3p、miR-205-5p 和 miR-124-3p 在 BC 患者的血清中表达下调与对照组相比。这些 miRNA 的 ROC 分析表明它们对识别 BC 患者具有显著的诊断准确性。此外,miR-155-5p 在 TNBC 中显著上调,可作为 TNBC 的指示性标志物。这项研究为开发具有潜在临床应用的非侵入性 miRNA 生物标志物具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4e6/11607072/c614d6e4ffe5/41598_2024_68758_Fig1_HTML.jpg

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