Tumor Suppressor miRNA-based Signatures in Triple Negative Breast Cancer: A Study Based on Big Data Analysis of Gene Expression Omnibus (GEO) Datasets and Its Validation.

Q2 Medicine

Asian Pacific Journal of Cancer Prevention Pub Date : 2025-06-01 DOI:10.31557/APJCP.2025.26.6.2087

Kavitha Unnikrishnan, Sivakumar Krishnankutty Chandrika, Ram Mohan Ram Kumar, Priya Srinivas

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引用次数: 0

Abstract

Background: Emerging evidence highlights the therapeutic potential of microRNAs (miRNAs) in cancer, positioning them as key molecular tools in personalized medicine. In this study, we aim to identify miRNAs as novel indicators of poor prognosis in Triple Negative Breast Cancer (TNBC) patients and to explore their potential therapeutic options for TNBC.

Materials and methods: Potent tumor suppressor miRNAs were obtained from four available datasets (GSE38167, GSE40049, GSE86278, GSE154255) of the Gene Expression Omnibus database comprising a total of 94 TNBC-positive and 40 normal tissue samples were analyzed using DESeq2 software. Further, TargetScan was used to predict the targets of differentially downregulated miRNAs and the functional and pathway enrichment analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) bioinformatics tool. The data obtained were validated by quantitative real-time PCR (qRT-PCR). Finally, survival analysis was performed in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort to check the impact of these miRNAs in TNBC patients.

Results: Differential expression analysis revealed that 110 miRNAs were upregulated and 243 miRNAs were downregulated in TNBC samples compared to the normal breast tissue samples. The top five downregulated miRNAs were miR-204, miR-6068, miR-139, miR-26a and miR-215. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology analysis showed that these miRNAs are involved in various hallmarks of cancer. Further validation using qRT-PCR analysis showed that miR-204, miR-139, and miR-26a were significantly downregulated in TNBC cell lines, MDA-MB-231, MDA-MB-468 and HCC1937 compared to non-tumorigenic cell line, MCF 10A. Kaplan-Meier analysis showed that the survival rate of patients with low miR-204 expression was significantly lower compared to the miR-204 upregulated group.

Conclusion: miR-204 can be a potential therapeutic molecule in TNBC. Strategies aimed at restoring the expression of miR-204 through miRNA replacement therapies could offer novel therapeutic approaches for TNBC patients.

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三阴性乳腺癌中基于肿瘤抑制mirna的特征：基于基因表达综合（GEO）数据集的大数据分析及其验证

背景：新出现的证据强调了microRNAs （miRNAs）在癌症中的治疗潜力，将其定位为个性化医疗的关键分子工具。在这项研究中，我们旨在确定mirna作为三阴性乳腺癌（TNBC）患者预后不良的新指标，并探索其潜在的TNBC治疗方案。材料和方法：从Gene Expression Omnibus数据库的四个可用数据集（GSE38167、GSE40049、GSE86278、GSE154255）中获得有效的肿瘤抑制mirna，共包含94个tnbc阳性组织样本和40个正常组织样本，使用DESeq2软件进行分析。此外，TargetScan用于预测差异下调mirna的靶标，并使用数据库注释，可视化和集成发现（DAVID）生物信息学工具进行功能和途径富集分析。采用实时荧光定量PCR （qRT-PCR）对所得数据进行验证。最后，在乳腺癌国际联盟分子分类学（METABRIC）队列中进行生存分析，以检查这些mirna对TNBC患者的影响。结果：差异表达分析显示，与正常乳腺组织样本相比，TNBC样本中有110个mirna上调，243个mirna下调。下调最多的5个mirna分别是miR-204、miR-6068、miR-139、miR-26a和miR-215。京都基因与基因组百科全书（KEGG）和基因本体分析表明，这些mirna参与了癌症的各种标志。通过qRT-PCR分析进一步验证表明，与非致瘤性细胞系MCF 10A相比，miR-204、miR-139和miR-26a在TNBC细胞系MDA-MB-231、MDA-MB-468和HCC1937中显著下调。Kaplan-Meier分析显示，miR-204低表达组患者的生存率明显低于miR-204上调组。结论：miR-204可能是一种潜在的TNBC治疗分子。旨在通过miRNA替代疗法恢复miR-204表达的策略可以为TNBC患者提供新的治疗方法。

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

Asian Pacific Journal of Cancer Prevention 医学-肿瘤学

CiteScore

2.80

自引率

0.00%

发文量

779

审稿时长

3 months

期刊介绍： Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: -Epidemiology, detection and screening. -Cellular research and bio-markers. -Identification of bio-targets and agents with novel mechanisms of action. -Optimal clinical use of existing anti-cancer agents, including combination therapies. -Radiation and surgery. -Palliative care. -Patient adherence, quality of life, satisfaction. -Health economic evaluations.