Functional Characterization of LTR12C as Regulators of Germ-Cell-Associated TA-p63 in U87-MG and T98-G In Vitro Models
Glioblastoma multiforme (GBM) is a deadly disease known for its genetic heterogeneity. LTR12C is an endogenous retrovirus-derived regulator of pro-apoptotic genes and is normally silenced by epigenetic regulation. In this study, we found that the treatment of two glioblastoma cell lines, T98-G and U...
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2025-06-01
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| author | Lucia Meola Sohum Rajesh Shetty Angelo Peschiaroli Claudio Sette Camilla Bernardini |
| author_facet | Lucia Meola Sohum Rajesh Shetty Angelo Peschiaroli Claudio Sette Camilla Bernardini |
| author_sort | Lucia Meola |
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| description | Glioblastoma multiforme (GBM) is a deadly disease known for its genetic heterogeneity. LTR12C is an endogenous retrovirus-derived regulator of pro-apoptotic genes and is normally silenced by epigenetic regulation. In this study, we found that the treatment of two glioblastoma cell lines, T98-G and U87-MG, with DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors activated LTR12C expression. Combined treatment with these epigenetic drugs exerted a synergistic action on the LTR12C activation in both cell lines, while treatment with each drug as a single agent had a far weaker effect. A strong induction of the expression of the TP63 gene was seen in both cell lines, with the pro-apoptotic isoform GTA-p63 accounting for most of this increase. Coherently, downstream targets of p63, such as p21 and PUMA, were also induced by the combined treatment. Furthermore, we observed a significant reduction in the GBM cell growth and viability following the dual DNMT/HDAC inhibition. These findings reveal that the reactivation of LTR12C expression has the potential to modulate survival pathways in glioblastoma and provide information regarding possible epigenetic mechanisms that can be used to treat this deadly disease. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-5c442b869c274833ba06aab6730b2a8b2025-08-20T03:46:38ZengMDPI AGCells2073-44092025-06-01141185210.3390/cells14110852Functional Characterization of LTR12C as Regulators of Germ-Cell-Associated TA-p63 in U87-MG and T98-G In Vitro ModelsLucia Meola0Sohum Rajesh Shetty1Angelo Peschiaroli2Claudio Sette3Camilla Bernardini4Department of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Heart, 00168 Rome, ItalyFaculty of Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, ItalyInstitute of Translational Pharmacology (IFT), CNR, Via Fosso del Cavaliere 100, 00133 Rome, ItalyDepartment of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Heart, 00168 Rome, ItalyDepartment of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Heart, 00168 Rome, ItalyGlioblastoma multiforme (GBM) is a deadly disease known for its genetic heterogeneity. LTR12C is an endogenous retrovirus-derived regulator of pro-apoptotic genes and is normally silenced by epigenetic regulation. In this study, we found that the treatment of two glioblastoma cell lines, T98-G and U87-MG, with DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors activated LTR12C expression. Combined treatment with these epigenetic drugs exerted a synergistic action on the LTR12C activation in both cell lines, while treatment with each drug as a single agent had a far weaker effect. A strong induction of the expression of the TP63 gene was seen in both cell lines, with the pro-apoptotic isoform GTA-p63 accounting for most of this increase. Coherently, downstream targets of p63, such as p21 and PUMA, were also induced by the combined treatment. Furthermore, we observed a significant reduction in the GBM cell growth and viability following the dual DNMT/HDAC inhibition. These findings reveal that the reactivation of LTR12C expression has the potential to modulate survival pathways in glioblastoma and provide information regarding possible epigenetic mechanisms that can be used to treat this deadly disease.https://www.mdpi.com/2073-4409/14/11/852epigeneticsLTR12CglioblastomaGTA-p63p21 |
| spellingShingle | Lucia Meola Sohum Rajesh Shetty Angelo Peschiaroli Claudio Sette Camilla Bernardini Functional Characterization of LTR12C as Regulators of Germ-Cell-Associated TA-p63 in U87-MG and T98-G In Vitro Models Cells epigenetics LTR12C glioblastoma GTA-p63 p21 |
| title | Functional Characterization of LTR12C as Regulators of Germ-Cell-Associated TA-p63 in U87-MG and T98-G In Vitro Models |
| title_full | Functional Characterization of LTR12C as Regulators of Germ-Cell-Associated TA-p63 in U87-MG and T98-G In Vitro Models |
| title_fullStr | Functional Characterization of LTR12C as Regulators of Germ-Cell-Associated TA-p63 in U87-MG and T98-G In Vitro Models |
| title_full_unstemmed | Functional Characterization of LTR12C as Regulators of Germ-Cell-Associated TA-p63 in U87-MG and T98-G In Vitro Models |
| title_short | Functional Characterization of LTR12C as Regulators of Germ-Cell-Associated TA-p63 in U87-MG and T98-G In Vitro Models |
| title_sort | functional characterization of ltr12c as regulators of germ cell associated ta p63 in u87 mg and t98 g in vitro models |
| topic | epigenetics LTR12C glioblastoma GTA-p63 p21 |
| url | https://www.mdpi.com/2073-4409/14/11/852 |
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