Regulation of the THRA gene, encoding the thyroid hormone nuclear receptor TR alpha 1, in intestinal lesions
| العنوان: | Regulation of the THRA gene, encoding the thyroid hormone nuclear receptor TR alpha 1, in intestinal lesions |
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| المؤلفون: | Maria Virginia Giolito, Théo La Rosa, Diana Farhat, Serguei Bodoirat, Gabriela D. A. Guardia, Claire Domon‐Dell, Pedro A. F. Galante, Jean‐Noel Freund, Michelina Plateroti |
| المساهمون: | Basic (bio-) Medical Sciences, Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospital Sírio-Libanês [São Paulo, Brazil], univOAK, Archive ouverte |
| المصدر: | Molecular Oncology Molecular Oncology, 2022, ⟨10.1002/1878-0261.13298⟩ |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Thyroid Hormones, Receptors, Thyroid Hormone, Genes, erbA, General Medicine, Mice, Oncology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, Molecular Medicine, Humans, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Colorectal Neoplasms, Thyroid Hormone Receptors alpha |
| الوصف: | The THRA gene, encoding the thyroid hormone nuclear receptor TRα1, is expressed in an increasing gradient at the bottom of intestinal crypts, overlapping with high Wnt and Notch activities. Importantly, THRA is upregulated in colorectal cancers, particularly in the high-Wnt molecular subtype. The basis of this specific and/or altered expression pattern has remained unknown. To define the mechanisms controlling THRA transcription and TRα1 expression, we used multiple in vitro and ex vivo approaches. Promoter analysis demonstrated that transcription factors important for crypt homeostasis and altered in colorectal cancers, such as transcription factor 7-like 2 (TCF7L2; Wnt pathway), recombining binding protein suppressor of hairless (RBPJ; Notch pathway), and homeobox protein CDX2 (epithelial cell identity), modulate THRA activity. Specifically, although TCF7L2 and CDX2 stimulated THRA, RBPJ induced its repression. In-depth analysis of the Wnt-dependent increase showed direct regulation of the THRA promoter in cells and of TRα1 expression in murine enteroids. Given our previous results on the control of the Wnt pathway by TRα1, our new results unveil a complex regulatory loop and synergy between these endocrine and epithelial-cell-intrinsic signals. Our work describes, for the first time, the regulation of the THRA gene in specific cell and tumor contexts. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1574-7891 1878-0261 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::14e089c0c8ed1dc67eab9d3bc26196f5 https://hdl.handle.net/20.500.14017/d249ccce-8538-4605-aaa5-2a2669add328 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....14e089c0c8ed1dc67eab9d3bc26196f5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15747891 18780261 |
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