Previously, we have reported that the dysregulation of ketogenesis plays an important role in the carcinogenesis of clear cell renal cell carcinoma (ccRCC). Here, we demonstrate decreased expression of the HMGCS2 gene in ccRCC, a critical enzyme for the synthesis of the ketone body β-hydroxybutyrate (β-OHB). We found that the reduced transcription of the HMGCS2 gene in ccRCC cells was significantly correlated to a higher relative methylation rate in its promotor region. The higher methylation rate in the region of the transcription start site and 1st exon of the HMGCS2 gene was, in turn, correlated with a worse clinical outcome for patients. The transcription of HMGCS2 was possible to restore by treatment with 5-aza-2'-deoxycytidine and with the histone deacetylase inhibitor β-OHB. Therefore, the low levels of the HMGCS2 enzyme in ccRCC may be the consequence of hypermethylation of the HMGCS2 promotor. The ensuing reduction in the ketone body levels further suppresses the transcription of HMGCS2 via a feedback loop. Ectopic expression of HMGCS2 attenuates the migration and invasion of ccRCC but does not affect the proliferative capacity of ccRCC cells in vitro. In addition, we showed that ectopic expression of HMGCS2 boosts the intracellular levels of β-OHB and that exogenously applied β-OHB suppresses the motility and invasion of ccRCC. Our study reveals crosstalk between genes that regulate metabolism and their metabolites, thus providing a better understanding of the epigenetic mechanism involved in ccRCC carcinogenesis and suggesting opportunities for metabolic therapy of tumors. Initially, we suggest that the mRNA level of HMGCS2 could serve as a potentially valuable diagnostic (AUC = 0.918, p < 0.001) and prognostic biomarker.
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http://dx.doi.org/10.1016/j.prp.2021.153622 | DOI Listing |
Heliyon
November 2024
Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará (UFPA), Av. Augusto Correa, 01, 66075-110, Brazil.
Poult Sci
November 2024
Key Laboratory for Animal Genetics & Molecular Breeding of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, PR China. Electronic address:
Residual feed intake (RFI) has recently gained attention as a key indicator of feed efficiency in poultry. In this study, 800 slow-growing ducks with similar initial body weights were reared in an experimental facility until they were culled at 42 d of age. Thirty high RFI (HRFI) and 30 low RFI (LRFI) birds were selected to evaluate their growth performance, carcass characteristics, and muscle development.
View Article and Find Full Text PDFAnim Nutr
December 2024
Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, College of Life Science and Engineering, Foshan University, Foshan 528225, China.
Epigenomics
December 2024
Division of Cardiology, Departments of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Aim: Diabetic cardiomyopathy (DbCM), a complex metabolic disease, greatly threatens human health due to therapeutic limitations. Multi-omics approaches facilitate the elucidation of its intrinsic pathological changes.
Methods: Metabolomics, RNA-seq, proteomics, and assay of transposase-accessible chromatin (ATAC-seq) were utilized to elucidate multidimensional molecular alterations in DbCM.
J Pharm Biomed Anal
February 2025
Key Laboratory of Tropical Translational Medicine of Ministry of Education & Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health, International Advanced Functional Omics Platform, Scientific Experiment Center, Hainan Engineering Research Center for Biological Sample Resources of Major Diseases, Hainan Medical University, Xueyuan Road 3, Haikou 571199, China; Graduate School, College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China. Electronic address:
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