Methylation of mitochondrial DNA displacement loop region regulates mitochondrial copy number in colorectal cancer
نویسندگان
چکیده
It is not established whether de‑methylation of the displacement loop (D‑loop) region if mitochondrial DNA (mtDNA) directly influences mtDNA copy number and further alters the cell cycle, apoptosis and cell proliferation in colorectal cancer. The current study employed cell viability assays, cell cycle analysis, and mtDNA methylation analysis using 5 colorectal cancer cell lines. The present results demonstrated that 5‑aza‑2'‑deoxycytidine (5‑AZA), a DNA hypomethylating agent, significantly increased proliferation of Lovo and Colo‑205 colorectal cancer cell lines. In Colo‑205 cells, the proportion of G0/G1 phase cells was increased following 5‑AZA treatment. Additionally, the apoptosis rate in Colo‑205 cells was decreased by 5‑AZA treatment. Compared with their controls, a significantly higher mtDNA copy number was observed in Colo‑205 and Lovo cells following 5‑AZA treatment. Notably, the Colo‑205 and Lovo cells had relatively higher methylation levels at the 4 and 6th/7th CpG sites of D‑loop region, respectively, compared with the levels at the corresponding sites following 5‑AZA treatment. However, in HCT116, SW480, LS‑174T, and HT‑29 cells, 5‑AZA treatment did not induce a significant change in proliferation, cell cycle, apoptosis and mtDNA copy number. Demethylation at the 4 and 6th/7th CpG sites of the D‑loop region of HCT116, SW480, LS‑174T and HT‑29 cells was not observed following 5‑AZA treatment. In conclusion, de‑methylation of specific sites on CpG islands of D‑loop promoter may lead to the elevation of mtDNA copy number in colorectal cancer, triggering alterations in biological behaviors, including increased cell proliferation, reduced apoptosis and a relative cell cycle arrest in G0/G1 phase.
منابع مشابه
De-methylation of displacement loop of mitochondrial DNA is associated with increased mitochondrial copy number and nicotinamide adenine dinucleotide subunit 2 expression in colorectal cancer.
DNA methylation occurs in the displacement loop (D-loop) region of mammals; however, D-loop regions of certain tumor tissue types were found to be de‑methylated. Whether hypomethylation of the D‑loop region is involved in the regulation of the mitochondrial DNA (mtDNA) copy number and nicotinamide adenine dinucleotide subunit 2 (ND‑2) expressions in colorectal cancer has remained elusive. In th...
متن کاملGenetic Analysis of D-Loop Region of Mitochondrial DNA Sequence in Iranian Patients with Familial Adenomatous Polyposis (FAP): A Case-Control Study
Background and Objectives: Familial adenomatous polyposis (FAP) is an inherited disorder and a rare form of colorectal cancer. This disease appears equally in both sexes and its occurrence is more in the second or third decade of life. Mutations and alterations of the mitochondrial genome, especially the D-loop region, have been reported in various human tumors. But the exact role of these muta...
متن کاملSequence Variations of Mitochondrial DNA Displacement-Loop in Iranian Indigenous Sheep Breeds
Mitochondrial DNA (mtDNA) has been used extensively to study population genetics because it has the unique features of maternal inheritance, a relatively fast rate of evolution and lack of recombination. A total of 82 unrelated sheep from 10 Iranian indigenous sheep breeds were investigated to determinate the maternal genetic diversity using a sequence of a 685 bp segment of the displacement lo...
متن کاملAssessment of mitochondrial DNA copy number in peripheral blood leukocyte of opiate abusers and healthy individuals
Background: Based on the studies, variation in the mitochondrial DNA (mtDNA) copy number in peripheral blood leukocytes is associated with increased susceptibility to diseases including cancer. Opiate abusers are at high risk for diseases. In this study, we measured the mtDNA copy number in peripheral blood leukocytes in a group of opiate abusers compared with those in healthy individuals. Met...
متن کاملRole of Mitochondria in Ataxia-Telangiectasia: Investigation of Mitochondrial Deletions and Haplogroups
Ataxia-Telangiectasia (AT) is a rare human neurodegenerative autosomal recessive multisystem disease that is characterized by a wide range of features including, progressive cerebellar ataxia with onset during infancy, occulocutaneous telangiectasia, susceptibility to neoplasia, occulomotor disturbances, chromosomal instability and growth and developmental abnormalities. Mitochondrial DNA (mtDN...
متن کامل