title: Correlation between increased ND2 expression and demethylated displacement             loop of mtDNA in colorectal cancer.
abstract: Change in cellular glucose metabolism is considered to be a biochemical             hallmark in cancer cells. The mitochondrion is the key organelle in which glucose             metabolism occurs. However, whether DNA methylation at the displacement loop (D-loop)             region of mitochondrial DNA (mtDNA) has an effect on the expression of the rate-limiting             enzyme, and, therefore, on oxidative phosphorylation in colorectal cancer remains             to be determined. Quantitative change in ND2 (a subunit of NADH) and the methylation             status of the D-loop were observed during the initiation and progression of colorectal             cancer. Furthermore, the possible correlations with clinicopathological stage             were also investigated. Tumor and corresponding non-cancerous tissues were surgically             resected from 44 colorectal cancer patients between 2008 and 2009. Cox IV expression             was quantified in all of the specimens, and the ND2 expression was calculated.             Quantitative changes in ND2 expression exhibited a significant increase. The average             relative ratios of ND2 content were 1.67±0.44 in the tumor tissues and 0.89±0.44             in the corresponding non-cancerous tissues (p<0.01). In addition, the D-loop             of most corresponding non-cancerous tissues was methylated and the percentage             was 79.5%, while this percentage was much smaller in the tumor tissues (11.4%).             Following correlation with clinicopathological data, changes in the ND2 expression             in the colorectal cancer exhibited a significant association with clinicopathological             stage. This increase was significant as early as in stage Ⅰ. Furthermore, the             ratios of unmethylated D-loop cases were increased in both tumor and corresponding             non-cancerous tissues, and the ND2 expression was also increased from stages Ⅰ             to Ⅳ. Our results indicate that demethylation of the D-loop plays a key role in             regulating ND2 expression during the initiation and/or progression of colorectal             cancer.
authors.affiliation: Department of Human Anatomy, College of Basic and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Shi
authors.initials: S
authors.lastname: Feng
authors.forename: Lili
authors.initials: L
authors.lastname: Xiong
authors.forename: Zhenni
authors.initials: Z
authors.lastname: Ji
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.forename: Huijun
authors.initials: H
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D004272:DNA, Mitochondrial / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009245:NADH Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D051381:Rats
chemical_list: D004272:DNA, Mitochondrial; D009245:NADH Dehydrogenase; C521326:NADH dehydrogenase subunit 2, human