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Background: Breast cancer is the most common malignancy among women worldwide, characterized by complex molecular and cellular heterogeneity. Despite advances in diagnosis and treatment, there is an urgent need to identify reliable biomarkers and therapeutic targets to improve early detection and personalized therapy. The OAS (2'-5'-oligoadenylate synthetase) family genes, known for their roles in antiviral immunity, have emerged as potential regulators in cancer biology. This study aimed to explore the diagnostic and functional relevance of OAS family genes in breast cancer.
Methodology: Breast cancer cell lines and controls were cultured under specific conditions, and DNA and RNA were extracted for downstream analyses. RT-qPCR, bisulfite sequencing, and Western blotting were employed to assess gene expression, promoter methylation, and knockdown efficiency of OAS family genes. Functional assays, including CCK-8, colony formation, and wound healing, evaluated cellular behaviors, while bioinformatics tools (UALCAN, GEPIA, HPA, OncoDB, cBioPortal, and others) validated findings and explored correlations with clinical data.
Results: The OAS family genes (OAS1, OAS2, OAS3, and OASL) were found to be significantly upregulated in breast cancer cell lines and tissues compared to normal controls. This overexpression was strongly associated with reduced promoter methylation. Receiver operating characteristic (ROC) analysis demonstrated high diagnostic accuracy, with area under the curve (AUC) values exceeding 0.93 for all four genes. Increased OAS expression correlated with advanced cancer stages and poor overall survival in breast cancer patients. Functional analysis revealed their involvement in critical biological processes, including immune modulation and oncogenic pathways. Silencing OAS genes in breast cancer cells significantly inhibited cell proliferation and colony formation, while unexpectedly enhancing migratory capacity. Additionally, correlations with immune cell infiltration, molecular subtypes, and drug sensitivity highlighted their potential roles in the tumor microenvironment and therapeutic response.
Conclusion: The findings of this study established OAS family genes as potential biomarkers and key players in breast cancer progression, offering promise as diagnostic biomarkers and therapeutic targets to address unmet clinical needs.
Download full-text PDF |
Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619215 | PMC |
http://dx.doi.org/10.1186/s41065-024-00353-9 | DOI Listing |
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