ArticleFrontiers in oncology2025
Multi-omics profiling of TGF-β isoforms and regulatory miRNAs in astrocytic tumors reveals TGF-β-3 as a prognostic biomarker.
Article in Frontiers in oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- MicroRNAs in Esophageal Cancer: Implications for Diagnosis, Progression, Prognosis and Chemoresistance.International journal of molecular sciences · 2026Review
- Multi-Layered Analysis of TGF-β Signaling and Regulation via DNA Methylation and microRNAs in Astrocytic Tumors.International journal of molecular sciences · 2025Article
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9 authors.
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Abstract
Background: Astrocytic tumors, particularly glioblastomas, are aggressive brain malignancies with poor prognosis. Transforming growth factor-beta (TGF-β) isoforms-TGF-β-1, TGF-β-2, and TGF-β-3-play critical roles in glioma progression, yet their isoform-specific expression patterns and regulatory mechanisms remain incompletely defined. This study aimed to evaluate the differential expression of TGF-β isoforms and their regulation by epigenetic mechanisms and microRNAs (miRNAs) across astrocytic tumor grades. Methods: Sixty-five astrocytic tumor samples (WHO grades 2-4) were analyzed. Gene and protein expression of TGF-β-1, -2, and -3 were assessed using reverse transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC). Promoter methylation was analyzed using methylation-specific PCR (MSPCR). Differentially expressed regulatory miRNAs were identified by microarray and in silico target prediction. Survival associations were evaluated by Kaplan-Meier and Cox regression analyses. Results: TGF-β-1 and TGF-β-3 were significantly upregulated in high-grade astrocytomas (p < 0.05), whereas TGF-β-2 showed no consistent changes. TGF-β-3 expression strongly correlated with poor survival (Exp(B) = 1.02644, p < 0.0001), while TGF-β-1 showed a weaker, non-significant association. Among regulatory miRNAs, hsa-miR-2278 (targeting TGF-β-3) was upregulated and significantly associated with worse survival (Exp(B) = 1.437, p = 0.008), while hsa-miR-3196 (targeting TGF-β-1) was downregulated and trended toward better prognosis (Exp(B) = 0.8897, p = 0.076). Conclusion: TGF-β-3 is a potent prognostic biomarker in astrocytic tumors and a promising candidate for targeted therapeutic intervention. Regulatory miRNAs such as hsa-miR-2278 and hsa-miR-3196 may serve as molecular modulators of TGF-β signaling and potential adjuncts in personalized glioma therapy. These findings warrant further investigation into miRNA-based therapeutics targeting the TGF-β axis in high-grade gliomas.
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