Unnikrishnan Kavitha, Krishnankutty Chandrika Sivakumar, Ram Kumar Ram Mohan, Srinivas Priya
Cancer Research Program, BRIC- Rajiv Gandhi Centre for Biotechnology (BRIC-RGCB), Thiruvananthapuram, 695014, India.
Manipal Academy of Higher Education (MAHE), Manipal 576104, India.
Asian Pac J Cancer Prev. 2025 Jun 1;26(6):2087-2095. doi: 10.31557/APJCP.2025.26.6.2087.
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.
背景：新出现的证据凸显了微小RNA（miRNA）在癌症治疗中的潜力，使其成为个性化医疗中的关键分子工具。在本研究中，我们旨在鉴定miRNA作为三阴性乳腺癌（TNBC）患者预后不良的新指标，并探索其对TNBC的潜在治疗选择。 材料与方法：从基因表达综合数据库的四个可用数据集（GSE38167、GSE40049、GSE86278、GSE154255）中获取强效肿瘤抑制性miRNA，这些数据集共包含94个TNBC阳性和40个正常组织样本，使用DESeq2软件进行分析。此外，使用TargetScan预测差异下调miRNA的靶标，并使用注释、可视化和综合发现数据库（DAVID）生物信息学工具进行功能和通路富集分析。通过定量实时PCR（qRT-PCR）对获得的数据进行验证。最后，在国际乳腺癌分子分类联盟（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。下调最明显的前五个miRNA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参与了癌症的各种特征。使用qRT-PCR分析进一步验证表明，与非致瘤细胞系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分析表明，miR-204表达低的患者生存率与miR-204上调组相比显著降低。 结论：miR-204可能是TNBC的潜在治疗分子。通过miRNA替代疗法恢复miR-204表达的策略可为TNBC患者提供新的治疗方法。
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