Selective targeting of genes regulated by zinc finger proteins in endometriosis and endometrioid adenocarcinoma by zinc niflumato complex with neocuproine
Abstract Inadequate angiogenesis of endometriotic implants stimulated by the inflammatory microenvironment in the uterine region leads to the development of gynecological diseases, which significantly reduce the fertility and vitality of young women. Angiogenic processes are controlled by factors wh...
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Nature Portfolio
2025-03-01
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| Online Access: | https://doi.org/10.1038/s41598-025-94249-x |
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| author | Ivana Špaková Lukáš Smolko Gabriela Sabolová Zuzana Badovská Katarína Kalinová Corina Madreiter-Sokolowski Wolfgang F. Graier Mária Mareková Janka Vašková Miroslava Rabajdová |
| author_facet | Ivana Špaková Lukáš Smolko Gabriela Sabolová Zuzana Badovská Katarína Kalinová Corina Madreiter-Sokolowski Wolfgang F. Graier Mária Mareková Janka Vašková Miroslava Rabajdová |
| author_sort | Ivana Špaková |
| collection | DOAJ |
| description | Abstract Inadequate angiogenesis of endometriotic implants stimulated by the inflammatory microenvironment in the uterine region leads to the development of gynecological diseases, which significantly reduce the fertility and vitality of young women. Angiogenic processes are controlled by factors whose activities are regulated at the gene level by reactive oxygen species (ROS), hypoxia-induced factors (HIFs), and zinc-finger proteins (ZnFs) or posttranscriptionally via non-coding RNAs. The cooperation of these factors is responsible for the manifestation of pathological stimuli in the form of endometriosis of the body of the uterus, ovaries, or peritoneum, from which endometrioid carcinoma can develop. Molecules that can control gene expression by their intercalation to target DNA sequence, such as [Zn(neo)(nif)2], could prevent the hyperactivation of pro-angiogenic pathways (decrease HIF-1α, VEGF-A, TGF-β1, COX2, and ANG2/ANG1), reduce the formation of ROS, and reduce the risk of uterine neoplasticity. The NSAID-metal complex [Zn(neo)(nif)2] shows an ability to intercalate into ZNF3-7 target DNA sequence at a higher rate, which could explain its effect on genes regulated by this transcription factor. In addition, [Zn(neo)(nif)2] affects ROS production and Ca2+ level, possibly pointing to mitochondrial dysfunction as a potential cause for the described apoptosis. |
| format | Article |
| id | doaj-art-e67d2c29bfa0432ebb1f65a655960e52 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-e67d2c29bfa0432ebb1f65a655960e522025-08-20T03:41:12ZengNature PortfolioScientific Reports2045-23222025-03-0115111910.1038/s41598-025-94249-xSelective targeting of genes regulated by zinc finger proteins in endometriosis and endometrioid adenocarcinoma by zinc niflumato complex with neocuproineIvana Špaková0Lukáš Smolko1Gabriela Sabolová2Zuzana Badovská3Katarína Kalinová4Corina Madreiter-Sokolowski5Wolfgang F. Graier6Mária Mareková7Janka Vašková8Miroslava Rabajdová9Department of Medical and Clinical Biochemistry, P. J. Šafárik University in KošiceDepartment of Medical and Clinical Biochemistry, P. J. Šafárik University in KošiceDepartment of Medical and Clinical Biochemistry, P. J. Šafárik University in KošiceDepartment of Medical and Clinical Biochemistry, P. J. Šafárik University in KošiceGottfried Schatz Research Center for Cell Signaling, Metabolism and Aging Molecular Biology and Biohemistry, Medical University of GrazGottfried Schatz Research Center for Cell Signaling, Metabolism and Aging Molecular Biology and Biohemistry, Medical University of GrazGottfried Schatz Research Center for Cell Signaling, Metabolism and Aging Molecular Biology and Biohemistry, Medical University of GrazDepartment of Medical and Clinical Biochemistry, P. J. Šafárik University in KošiceDepartment of Medical and Clinical Biochemistry, P. J. Šafárik University in KošiceDepartment of Medical and Clinical Biochemistry, P. J. Šafárik University in KošiceAbstract Inadequate angiogenesis of endometriotic implants stimulated by the inflammatory microenvironment in the uterine region leads to the development of gynecological diseases, which significantly reduce the fertility and vitality of young women. Angiogenic processes are controlled by factors whose activities are regulated at the gene level by reactive oxygen species (ROS), hypoxia-induced factors (HIFs), and zinc-finger proteins (ZnFs) or posttranscriptionally via non-coding RNAs. The cooperation of these factors is responsible for the manifestation of pathological stimuli in the form of endometriosis of the body of the uterus, ovaries, or peritoneum, from which endometrioid carcinoma can develop. Molecules that can control gene expression by their intercalation to target DNA sequence, such as [Zn(neo)(nif)2], could prevent the hyperactivation of pro-angiogenic pathways (decrease HIF-1α, VEGF-A, TGF-β1, COX2, and ANG2/ANG1), reduce the formation of ROS, and reduce the risk of uterine neoplasticity. The NSAID-metal complex [Zn(neo)(nif)2] shows an ability to intercalate into ZNF3-7 target DNA sequence at a higher rate, which could explain its effect on genes regulated by this transcription factor. In addition, [Zn(neo)(nif)2] affects ROS production and Ca2+ level, possibly pointing to mitochondrial dysfunction as a potential cause for the described apoptosis.https://doi.org/10.1038/s41598-025-94249-xEndometriosisEndometrioid adenocarcinoma[Zn(neo)(nif)2]AngiogenesisCa2+ROS |
| spellingShingle | Ivana Špaková Lukáš Smolko Gabriela Sabolová Zuzana Badovská Katarína Kalinová Corina Madreiter-Sokolowski Wolfgang F. Graier Mária Mareková Janka Vašková Miroslava Rabajdová Selective targeting of genes regulated by zinc finger proteins in endometriosis and endometrioid adenocarcinoma by zinc niflumato complex with neocuproine Scientific Reports Endometriosis Endometrioid adenocarcinoma [Zn(neo)(nif)2] Angiogenesis Ca2+ ROS |
| title | Selective targeting of genes regulated by zinc finger proteins in endometriosis and endometrioid adenocarcinoma by zinc niflumato complex with neocuproine |
| title_full | Selective targeting of genes regulated by zinc finger proteins in endometriosis and endometrioid adenocarcinoma by zinc niflumato complex with neocuproine |
| title_fullStr | Selective targeting of genes regulated by zinc finger proteins in endometriosis and endometrioid adenocarcinoma by zinc niflumato complex with neocuproine |
| title_full_unstemmed | Selective targeting of genes regulated by zinc finger proteins in endometriosis and endometrioid adenocarcinoma by zinc niflumato complex with neocuproine |
| title_short | Selective targeting of genes regulated by zinc finger proteins in endometriosis and endometrioid adenocarcinoma by zinc niflumato complex with neocuproine |
| title_sort | selective targeting of genes regulated by zinc finger proteins in endometriosis and endometrioid adenocarcinoma by zinc niflumato complex with neocuproine |
| topic | Endometriosis Endometrioid adenocarcinoma [Zn(neo)(nif)2] Angiogenesis Ca2+ ROS |
| url | https://doi.org/10.1038/s41598-025-94249-x |
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