Identification of super-enhancer-associated transcription factors regulating glucose metabolism in poorly differentiated thyroid carcinoma
Document title: Identification of super-enhancer-associated transcription factors regulating glucose metabolism in poorly differentiated thyroid carcinoma
Journal: Genetics and molecular biology
Database: PERIÓDICA
System number: 000459258
ISSN: 1415-4757
Authors: 1
2
3
3
Institutions: 1Tianjin Hospital, Endocrinology Department, Tianjin. China
280th Group Military Hospital, Endocrinology Department, Weifang, Shandong. China
3XingTai Medical College, Basic Experiment Center, Xingtai, Hebei. China
Year:
Volumen: 45
Number: 3
Country: Brasil
Language: Inglés
Document type: Artículo
Approach: Analítico, descriptivo
English abstract This study aimed to uncover transcription factors that regulate super-enhancers involved in glucose metabolism reprogramming in poorly differentiated thyroid carcinoma (PDTC). TCA cycle and pyruvate metabolism were significantly enriched in PDTC. Differentially expressed genes in PDTC vs. normal control tissues were located in key steps in TCA cycle and pyruvate metabolism. A total of 23 upregulated genes localized in TCA cycle and pyruvate metabolism were identified as super-enhancer-controlled genes. Transcription factor analysis of these 23 super-enhancer-controlled genes related to glucose metabolism was performed, and 20 transcription factors were obtained, of which KLF12, ZNF281 and RELA had a significant prognostic impact. Regulatory network of KLF12, ZNF281 and RELA controlled the expression of these four prognostic target genes (LDHA, ACLY, ME2 and IDH2). In vitro validation showed that silencing of KLF12, ZNF281 and RELA suppressed proliferation, glucose uptake, lactate production and ATP level, but increased ADP/ATP ratio in PDTC cells. In conclusion, KLF12, ZNF281 and RELA were identified as the key transcription factors that regulate super-enhancer-controlled genes related to glucose metabolism in PDTC. Our findings contribute to a deeper understanding of the regulatory mechanisms associated with glucose metabolism in PDTC, and advance the theoretical development of PDTC-targeted therapies
Disciplines: Medicina
Keyword: Oncología,
Factores de transcripción,
Glucosa,
Carcinoma,
Tiroides
Keyword: Oncology,
Transcription factors,
Glucose,
Carcinoma,
Thyroid
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