Multi-omics profiling of TGF-β isoforms and regulatory miRNAs in astrocytic tumors reveals TGF-β-3 as a prognostic biomarker
BackgroundAstrocytic 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 mech...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1592685/full |
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| author | Klaudia Skóra Klaudia Skóra Damian Strojny Damian Strojny Damian Strojny Dawid Sobański Dawid Sobański Rafał Staszkiewicz Rafał Staszkiewicz Rafał Staszkiewicz Kamil Bryś Paweł Gogol Paweł Gogol Paweł Gogol Paweł Gogol Krzysztof Bereza Krzysztof Bereza Michalina Masternak Beniamin Oskar Grabarek Beniamin Oskar Grabarek |
| author_facet | Klaudia Skóra Klaudia Skóra Damian Strojny Damian Strojny Damian Strojny Dawid Sobański Dawid Sobański Rafał Staszkiewicz Rafał Staszkiewicz Rafał Staszkiewicz Kamil Bryś Paweł Gogol Paweł Gogol Paweł Gogol Paweł Gogol Krzysztof Bereza Krzysztof Bereza Michalina Masternak Beniamin Oskar Grabarek Beniamin Oskar Grabarek |
| author_sort | Klaudia Skóra |
| collection | DOAJ |
| description | BackgroundAstrocytic 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.MethodsSixty-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.ResultsTGF-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).ConclusionTGF-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. |
| format | Article |
| id | doaj-art-82aa628d4c7a4a7ab0439ede886e4fce |
| institution | DOAJ |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-82aa628d4c7a4a7ab0439ede886e4fce2025-08-20T03:21:43ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-06-011510.3389/fonc.2025.15926851592685Multi-omics profiling of TGF-β isoforms and regulatory miRNAs in astrocytic tumors reveals TGF-β-3 as a prognostic biomarkerKlaudia Skóra0Klaudia Skóra1Damian Strojny2Damian Strojny3Damian Strojny4Dawid Sobański5Dawid Sobański6Rafał Staszkiewicz7Rafał Staszkiewicz8Rafał Staszkiewicz9Kamil Bryś10Paweł Gogol11Paweł Gogol12Paweł Gogol13Paweł Gogol14Krzysztof Bereza15Krzysztof Bereza16Michalina Masternak17Beniamin Oskar Grabarek18Beniamin Oskar Grabarek19Department of Neurological Rehabilitation, District Hospital of St. Padre Pio in Sędziszów Małopolski, Sędziszów Małopolski, PolandCollegium Medicum, WSB University, Dąbrowa Górnicza, PolandCollegium Medicum, WSB University, Dąbrowa Górnicza, PolandDepartment of Neurology, New Medical Techniques Specialist Hospital of St. Family in Rudna Mała, Rzeszow, PolandInstitute of Health Care, National Academy of Applied Sciences in Przemyśl, Przemyśl, PolandCollegium Medicum, WSB University, Dąbrowa Górnicza, PolandDepartment of Neurosurgery, St. Raphael Hospital, Krakow, PolandCollegium Medicum, WSB University, Dąbrowa Górnicza, PolandDepartment of Neurosurgery, 5th Military Clinical Hospital with the SP ZOZ Polyclinic in Krakow, Krakow, PolandDepartment of Neurosurgery, Faculty of Medicine in Zabrze, Academy of Silesia in Katowice, Katowice, PolandDepartment of Neurosurgery, Faculty of Medicine in Zabrze, Academy of Silesia in Katowice, Katowice, PolandCollegium Medicum, WSB University, Dąbrowa Górnicza, PolandDepartment of Anesthesiology and Intensive Care, Our Lady of Perpetual Help Hospital in Wołomin, Wołomin, PolandDepartment of Trauma and Orthopedic Surgery, Our Lady of Perpetual Help Hospital in Wołomin, Wołomin, Poland0Pain Treatment Clinic, Our Lady of Perpetual Help Hospital in Wołomin, Wołomin, Poland1Department of Mother and Child Health, Faculty of Health Sciences, Institute of Nursing and Midwifery, Jagiellonian University Medical College, Krakow, Poland2Department of Brachytherapy, Jagiellonian University Medical College, Krakow, Poland3Silesian Center for Rehabilitation and Manual Therapy Revita in Mysłowice, Mysłowice, PolandCollegium Medicum, WSB University, Dąbrowa Górnicza, Poland4Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski University, Cracow, PolandBackgroundAstrocytic 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.MethodsSixty-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.ResultsTGF-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).ConclusionTGF-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.https://www.frontiersin.org/articles/10.3389/fonc.2025.1592685/fulltransforming growth factor beta 1-3astrocytic tumorssurvival analysismicro RNAmolecular marker |
| spellingShingle | Klaudia Skóra Klaudia Skóra Damian Strojny Damian Strojny Damian Strojny Dawid Sobański Dawid Sobański Rafał Staszkiewicz Rafał Staszkiewicz Rafał Staszkiewicz Kamil Bryś Paweł Gogol Paweł Gogol Paweł Gogol Paweł Gogol Krzysztof Bereza Krzysztof Bereza Michalina Masternak Beniamin Oskar Grabarek Beniamin Oskar Grabarek Multi-omics profiling of TGF-β isoforms and regulatory miRNAs in astrocytic tumors reveals TGF-β-3 as a prognostic biomarker Frontiers in Oncology transforming growth factor beta 1-3 astrocytic tumors survival analysis micro RNA molecular marker |
| title | Multi-omics profiling of TGF-β isoforms and regulatory miRNAs in astrocytic tumors reveals TGF-β-3 as a prognostic biomarker |
| title_full | Multi-omics profiling of TGF-β isoforms and regulatory miRNAs in astrocytic tumors reveals TGF-β-3 as a prognostic biomarker |
| title_fullStr | Multi-omics profiling of TGF-β isoforms and regulatory miRNAs in astrocytic tumors reveals TGF-β-3 as a prognostic biomarker |
| title_full_unstemmed | Multi-omics profiling of TGF-β isoforms and regulatory miRNAs in astrocytic tumors reveals TGF-β-3 as a prognostic biomarker |
| title_short | Multi-omics profiling of TGF-β isoforms and regulatory miRNAs in astrocytic tumors reveals TGF-β-3 as a prognostic biomarker |
| title_sort | multi omics profiling of tgf β isoforms and regulatory mirnas in astrocytic tumors reveals tgf β 3 as a prognostic biomarker |
| topic | transforming growth factor beta 1-3 astrocytic tumors survival analysis micro RNA molecular marker |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1592685/full |
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