دورية أكاديمية
أعرض في EDS

DNA Methylation of TGFβ Target Genes: Epigenetic Control of TGFβ Functional Duality in Liver Cancer.

التفاصيل البيبلوغرافية
العنوان: DNA Methylation of TGFβ Target Genes: Epigenetic Control of TGFβ Functional Duality in Liver Cancer.
المؤلفون: Bévant K; Centre de Lutte Contre le Cancer Eugène Marquis, Inserm, University of Rennes 1, UMR_S 1242, COSS (Chemistry, Oncogenesis Stress Signaling), 35042 Rennes, France., Desoteux M; Centre de Lutte Contre le Cancer Eugène Marquis, Inserm, University of Rennes 1, UMR_S 1242, COSS (Chemistry, Oncogenesis Stress Signaling), 35042 Rennes, France., Abdel Wahab AHA; Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11796, Egypt., Abdel Wahab SA; Medical Laboratory Department, Students Hospital, Cairo University, Cairo 11796, Egypt., Metwally AM; Medical Laboratory Technology Department, College of Applied Health Science Technology, Misr University for Science and Technology (MUST), Al-Motamayez District, 6th of October P.O. Box 77, Egypt., Coulouarn C; Centre de Lutte Contre le Cancer Eugène Marquis, Inserm, University of Rennes 1, UMR_S 1242, COSS (Chemistry, Oncogenesis Stress Signaling), 35042 Rennes, France.
المصدر: Cells [Cells] 2021 Aug 26; Vol. 10 (9). Date of Electronic Publication: 2021 Aug 26.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مواضيع طبية MeSH: Carcinoma, Hepatocellular/*genetics , Epigenesis, Genetic/*genetics , Transforming Growth Factor beta/*genetics, Carcinoma, Hepatocellular/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Cell Transformation, Neoplastic/genetics ; DNA Methylation/physiology ; Decitabine/pharmacology ; Epigenesis, Genetic/drug effects ; Epithelial-Mesenchymal Transition/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Liver/pathology ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Neoplasm Recurrence, Local/genetics ; Signal Transduction/genetics ; Snail Family Transcription Factors/genetics ; Snail Family Transcription Factors/metabolism ; Transcription Factors/metabolism ; Transforming Growth Factor beta/metabolism
مستخلص: Transforming growth factor beta (TGFβ) plays a key role in liver carcinogenesis. However, its action is complex, since TGFβ exhibits tumor-suppressive or oncogenic properties, depending on the tumor stage. At an early stage TGFβ exhibits cytostatic features, but at a later stage it promotes cell growth and metastasis, as a potent inducer of epithelial to mesenchymal transition (EMT). Here, we evaluated DNA methylation as a possible molecular mechanism switching TGFβ activity toward tumor progression in hepatocellular carcinoma (HCC). We report that decitabine, a demethylating agent already used in the clinic for the treatment of several cancers, greatly impairs the transcriptional response of SNU449 HCC cells to TGFβ. Importantly, decitabine was shown to induce the expression of EMT-related transcription factors (e.g., SNAI1/2 , ZEB1/2 ). We also report that the promoter of SNAI1 was hypomethylated in poor-prognosis human HCC, i.e., associated with high grade, high AFP level, metastasis and recurrence. Altogether, the data highlight an epigenetic control of several effectors of the TGFβ pathway in human HCC possibly involved in switching its action toward EMT and tumor progression. Thus, we conclude that epidrugs should be carefully evaluated for the treatment of HCC, as they may activate tumor promoting pathways.
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معلومات مُعتمدة: recurrent funding Inserm, Université de Rennes 1, Ligue Contre le Cancer (CD22, CD35, CD85); Plan cancer INCa, and ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé) dans le cadre du Plan cancer (Non-coding RNA in cancerology: fundamental to translational); PhD fellowship Ligue Contre le Cancer (CD22) and Région Bretagne; project N° 39530VD Campus France in the framework of the Franco-Egyptian partnership IMHOTEP Hubert Curien program between Univ Rennes 1, Inserm and Faculty of Applied Medical Sciences Misr University for Science for science and technology
فهرسة مساهمة: Keywords: DNA methylation; EMT; TGFβ; epigenetics; hepatocellular carcinoma
المشرفين على المادة: 0 (SNAI1 protein, human)
0 (Snail Family Transcription Factors)
0 (Transcription Factors)
0 (Transforming Growth Factor beta)
776B62CQ27 (Decitabine)
تواريخ الأحداث: Date Created: 20210928 Date Completed: 20211119 Latest Revision: 20230921
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC8468746
DOI: 10.3390/cells10092207
PMID: 34571856
قاعدة البيانات: MEDLINE
الوصف
تدمد:2073-4409
DOI:10.3390/cells10092207