Archivos suplementarios
Palabras clave
salud
bioinformática
factores de transcripción
genes PDGF
Cómo citar
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Societal impact
Resumen
El factor de crecimiento derivado de plaquetas (PDGF) y sus receptores son vitales para una amplia gama de procesos fisiológicos como el desarrollo, la proliferación y la migración, así como para procesos patológicos como el crecimiento y la invasión de tumores. El objetivo de nuestro trabajo fue caracterizar in silico nuevos elementos reguladores cis (CRE) en las secuencias promotoras de genes PDGF para identificar los factores de transcripción (TF) asociados con estos sitios. Para caracterizar los CRE, recuperamos la secuencia promotora cercana al sitio de inicio de la transcripción (TSS) de la base de datos de promotores eucarióticos (EPD) ExPASy y realizamos una búsqueda y predicción in silico de nuevos CRE en las secuencias promotoras de los genes PDGF. Asimismo, evaluamos posibles factores de transcripción enriquecidos para estos CRE. Nuestro trabajo demostró la coexpresión en el glioblastoma del gen PDGFB y el factor de transcripción POU2F1, el cual se prevé que se una al gen PDGF, con una correlación moderada entre ambos (R² = 0,24). Se observaron asociaciones positivas similares entre el gen PDGFB y el factor de transcripción ZNF680 (R² = 0,21) y entre el gen PDGFB y el factor de transcripción FOXF1 (R² = 0,32). Estos hallazgos sugieren posibles relaciones entre el gen PDGFB y factores de transcripción específicos en el glioblastoma, aunque las interacciones reguladoras funcionales aún deben validarse experimentalmente. En general, los datos ponen de relieve patrones de coexpresión selectivos que involucran al gen PDGFB y a factores de transcripción candidatos. Estas observaciones proporcionan una base para investigar más a fondo las posibles relaciones transcripcionales en la biología del glioblastoma.
Referencias
Aleksander, S. A., Balhoff, J., Carbon, S., Cherry, J. M., Drabkin, H. J., Ebert, D., Feuermann, M., Gaudet, P., Harris, N. L., Hill, D. P., Lee, R., Mi, H., Moxon, S., Mungall, C. J., Muruganugan, A., Mushayahama, T., Sternberg, P. W., Thomas, P. D., Van Auken, K., Ramsey, J., Siegele, D. A., Chisholm, R. L., Fey, P., Aspromonte, M. C., Nugnes, M. V., Quaglia, F., Tosatto, S., Giglio, M., Westerfield, M. (2023). The Gene Ontology knowledgebase in 2023. Genetics, 224(1), 1-14. https://doi.org/10.1093/genetics/iyad031
Asano, Y., Kawase, T., Okabe, A., Tsutsumi, S., Ichikawa, H., Tatebe, S., Kitabayashi, I., Tashiro, F., Namiki, H., Kondo, T., Semba, K., Aburatani, H., Taya, Y., Nakagama, H., & Ohki, R. (2016). IER5 generates a novel hypo-phosphorylated active form of HSF1 and contributes to tumorigenesis. Scientific Reports, 6, 19174. https://doi.org/10.1038/srep19174
Bailey, T. L., Johnson, J., Grant, C. E., Noble, W. S. (2015). The MEME Suite. Nucleic Acids Research, 43(W1), W39-W49. https://doi.org/10.1093/nar/gkv416
Chen, X., Liu, L., Liu, P., Chen, Y., Lin, D., Yan, H., Yan, Q., Wang, Y., Qiu, Y., Fang, B., Huang, H., Qian, J., Zhao, Y., Du, Z., Zhang, Q., Li, X., Zheng, X., & Liu, Z. (2022). Discovery of Potent and Orally Bioavailable Platelet-Derived Growth Factor Receptor (PDGFR) Inhibitors for the Treatment of Osteosarcoma. Journal of Medicinal Chemistry, 65(7), 5374-5391. https://doi.org/10.1021/acs.jmedchem.1c01732
Choi, Y. S. & Sinha, S. (2006). Determination of the consensus DNA-binding sequence and a transcriptional activation domain for ESE-2. The Biochemical Journal, 398(3), 497-507. https://doi.org/10.1042/BJ20060375
de Villenfagne, L., Sablon, A., Demoulin, J.-B. (2024). PDGFRA K385 mutants in myxoid glioneuronal tumors promote receptor dimerization and oncogenic signaling. Scientific Reports, 14(1), 7204. https://doi.org/10.1038/s41598-024-57859-5
Ding, H., Wu, X., Kim, I., Tam, P. P. L., Koh, G. Y., Nagy, A. (2000). The mouse PDGFC gene: Dynamic expression in embryonic tissues during organogenesis. Mechanisms of Development, 96(2), 209-213. https://doi.org/10.1016/S0925-4773(00)00425-1
Dreos, R., Ambrosini, G., Groux, R., Perier, R. C., Bucher, P. (2017). The eukaryotic promoter database in its 30th year: Focus on non-vertebrate organisms. Nucleic Acids Research, 45(D1), D51-D55. https://doi.org/10.1093/nar/gkw1069
Ebersbach, C., Beier, A. M. K., Thomas, C., Erb, H. H. H. (2021). Impact of STAT proteins in tumor progress and therapy resistance in advanced and metastasized prostate cancer. Cancers, 13(19), 1-20. https://doi.org/10.3390/cancers13194854
Ferguson, M. W. J. (1988). Palate development. Development, 103(SUPPL.), 41-60. https://doi.org/10.1242/dev.103.supplement.41
Fornes, O., Castro-Mondragon, J. A., Khan, A., Van Der Lee, R., Zhang, X., Richmond, P. A., Modi, B. P., Correard, S., Gheorghe, M., Baranašić, D., Santana-Garcia, W., Tan, G., Chèneby, J., Ballester, B., Parcy, F., Sandelin, A., Lenhard, B., Wasserman, W. W., & Mathelier, A. (2020). JASPAR 2020: Update of the open-Access database of transcription factor binding profiles. Nucleic Acids Research, 48(D1), D87-D92. https://doi.org/10.1093/nar/gkz1001
Frederike Kramer, Jens Dernedde, Artur Mezheyeuski, Rudolf Tauber, Patrick Micke, Kai Kappert. (2020). Platelet-derived growth factor receptor β activation and regulation in murine myelofibrosis. Haematologica, 105(8 SE-Articles), 2083-2094. https://doi.org/10.3324/haematol.2019.226332
Gaudet, P., Livstone, M. S., Lewis, S. E., Thomas, P. D. (2011). Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in Bioinformatics, 12(5), 449-462. https://doi.org/10.1093/bib/bbr042
Gupta, S., Stamatoyannopoulos, J. A., Bailey, T. L., Noble, W. S. (2007). Quantifying similarity between motifs. Genome Biology, 8(2), article number R24. https://doi.org/10.1186/gb-2007-8-2-r24
Kang, G.-Y., Kim, E.-H., Lee, H.-J., Gil, N.-Y., Cha, H.-J., Lee, Y.-S. (2015). Heat shock factor 1, an inhibitor of non-homologous end joining repair. Oncotarget, 6(30), 29712-29724. https://doi.org/10.18632/oncotarget.5073
Kardas, G., Daszyńska-Kardas, A., Marynowski, M., Brząkalska, O., Kuna, P., Panek, M. (2020). Role of Platelet-Derived Growth Factor (PDGF) in Asthma as an Immunoregulatory Factor Mediating Airway Remodeling and Possible Pharmacological Target. Frontiers in Pharmacology, 11. https://doi.org/10.3389/fphar.2020.00047
Lee, K.-H., Bowen-Pope, D. F., Reed, R. R. (1990). Isolation and Characterization of the α Platelet-Derived Growth Factor Receptor from Rat Olfactory Epithelium. Molecular and Cellular Biology, 10(5), 2237-2246. https://doi.org/10.1128/mcb.10.5.2237-2246.1990
Lee, Y.-J., Kim, E.-H., Lee, J. S., Jeoung, D., Bae, S., Kwon, S. H., Lee, Y.-S. (2008). HSF1 as a mitotic regulator: phosphorylation of HSF1 by Plk1 is essential for mitotic progression. Cancer Research, 68(18), 7550-7560. https://doi.org/10.1158/0008-5472.CAN-08-0129
Li, D., Huang, L. T., Zhang, C. P., Li, Q., Wang, J. H. (2022). Insights Into the Role of Platelet-Derived Growth Factors: Implications for Parkinson’s Disease Pathogenesis and Treatment. Frontiers in Aging Neuroscience, 14, 1-30. https://doi.org/10.3389/fnagi.2022.890509
Li, T., Guo, T., Liu, H., Jiang, H., Wang, Y. (2021). Platelet-derived growth factor-BB mediates pancreatic cancer malignancy via regulation of the Hippo/Yes-associated protein signaling pathway. Oncology Reports, 45(1), 83-94. https://doi.org/10.3892/or.2020.7859
Pandey, P., Khan, F., Upadhyay, T. K., Seungjoon, M., Park, M. N., Kim, B. (2023). New insights about the PDGF/PDGFR signaling pathway as a promising target to develop cancer therapeutic strategies. Biomedicine and Pharmacotherapy, 161, 114491. https://doi.org/10.1016/j.biopha.2023.114491
Parra, E., Rojas, V., Ferreira, J., Hecht, P. (2021). Differential effects of Platelet-derived growth factor on c-Jun-N-Terminal Kinase and AP-1/ NF-kB activities in human glioblastoma T98G cells. Trends in Medicine, 21(4), 1-7. https://doi.org/10.15761/tim.1000277
Préfontaine, G. G., Walther, R., Giffin, W., Lemieux, M. E., Pope, L., Haché, R. J. (1999). Selective binding of steroid hormone receptors to octamer transcription factors determines transcriptional synergism at the mouse mammary tumor virus promoter. The Journal of Biological Chemistry, 274(38), 26713-26719. https://doi.org/10.1074/jbc.274.38.26713
Pulcinelli, F. M., Manzari, G., Bartoli, M., Faggioni, A., Mancusa, R. La, Pavan, A., Sansolini, T., Torrisi, M. R., & Gazzaniga, P. P. (1995). Mechanisms of the platelet proaggregating activity of human carcinoma a431 cells. Platelets, 6(4), 213-220. https://doi.org/10.3109/09537109509078458
Strubin, M., Newell, J. W., Matthias, P. (1995). OBF-1, a novel B cell-specific coactivator that stimulates immunoglobulin promoter activity through association with octamer-binding proteins. Cell, 80(3), 497-506. https://doi.org/10.1016/0092-8674(95)90500-6
Sun, Z., Cai, Y., Chen, Y., Jin, Q., Zhang, Z., Zhang, L., Li, Y., Huang, L., Wang, J., Yang, Y., Lv, Q., Han, Z., Xie, M., & Zhu, X. (2023). Ultrasound-targeted microbubble destruction promotes PDGF-primed bone mesenchymal stem cell transplantation for myocardial protection in acute Myocardial Infarction in rats. Journal of Nanobiotechnology, 21(1), 1-20. https://doi.org/10.1186/s12951-023-02204-7
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131(5), 861-872. https://doi.org/10.1016/j.cell.2007.11.019
Wysocka, J. & Herr, W. (2003). The herpes simplex virus VP16-induced complex: the makings of a regulatory switch. Trends in Biochemical Sciences, 28(6), 294-304. https://doi.org/10.1016/S0968-0004(03)00088-4
Xu, D., Zalmas, L. P., La Thangue, N. B. (2008). A transcription cofactor required for the heatshock response. EMBO Reports, 9(7), 662-669. https://doi.org/10.1038/embor.2008.70
Zhou, J., Ng, A. Y., Tymms, M. J., Jermiin, L. S., Seth, A. K., Thomas, R. S., Kola, I. (1998). A novel transcription factor, ELF5, belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13-15, a region subject to LOH and rearrangement in human carcinoma cell lines. Oncogene, 17(21), 2719-2732. https://doi.org/10.1038/sj.onc.1202198
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