Dynamic changes in DNA methylation and hydroxymethylation revealed the transformation of advanced adenoma into colorectal carcinoma

• Published in: Clinical and translational medicine Vol. 13; no. 3; pp. e1202 - n/a
• Main Authors: Dang, Yanqi, Xu, Ruohui, Pan, Jiashu, Xiao, Xiaoli, Zhang, Shengan, Zhou, Wenjun, Xu, Yangxian, Ji, Guang
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-03-2023; John Wiley and Sons Inc; Wiley
• Subjects: Biosynthesis; Cell growth; Colorectal cancer; Colorectal Neoplasms - genetics; DNA methylation; DNA Methylation - genetics; Humans; Letter to the Editor; Metabolism; Mortality; Proteins; Tumors; China
• ISSN: 2001-1326; 2001-1326
• DOI: 10.1002/ctm2.1202

DNA 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) could play major roles in CRC.4,5 A single-tube methylation-specific quantitative polymerase chain reaction (PCR) assay could be a good predictor of CRC recurrence,4 and 5-hmC levels of zw10 kinetochore protein could have a high diagnostic performance for early-stage CRC.5 However, the functions of 5mC and 5hmC in AA-CRC transformation remain unclear. [...]we conducted an integrated analysis of 5mC and 5hmC to elucidate the mechanism underlying AA-CRC transformation. The levels of five genes (ANO10, SUCLG2, PPARGC1A, LRBA, and ATP8A1) were positively correlated with the overall survival of patients with CRC (Figure S2). [...]compared with the AA group, mRNA and protein levels of PPARGC1A, LRBA, and ATP8A1 but not ANO10 and SUCLG2 were both markedly decreased in the CRC group (Figure 3B–F). Studies have shown that PPARGC1A mediates mitochondrial biogenesis and energy metabolism to regulate tumourigenesis in CRC.8,9 Our results also showed that PPARGC1A was markedly decreased in CRC, and PPARGC1A overexpression inhibited cell proliferation, invasion, and migration in HCT116 cells (Figure 4K,L; Figure S4F–H). [...]PPARGC1A expression was positively correlated with activated dendritic cells, memory resting CD4 T cells, and also related to energy metabolism and mitochondrial gene expression (Figure S4I–K; Additional File 5).