Epigenetic alteration of mitochondrial biogenesis regulatory genes in arsenic exposed individuals (with and without skin lesions) and in skin cancer tissues: A case control study

Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications

“…Mitochondrial DNA content and mitochondrial mass both increase during the transition from normal tissue to hyperplasia and malignancy, as indicated by Lamb et al [314] investigation using human breast cancer MCF7 cells and normal and cancer cells from various tissues. Similarly, chronic exposure to arsenic increases mitochondrial DNA copy number, mitochondrial toxicity, and oxidative stress in PBMC [249] and arsenic-induced skin cancers [248]. Epigenetic alterations play crucial roles linking arsenic-induced mitochondrial biogenesis and arsenical skin carcinogenesis.…”

“…Hypomethylation of both the D-loop and Nd6, as well as expression of ND6, increases with the urinary level of arsenic [249]. The mitochondrial biogenesis functions of the D-loop are regulated by the transcription factor TFAM (Transcription Factor A, Mitochondrial), which is transcribed from its nuclear gene, and also hypomethylated and expressed in PBMC in arsenic exposed populations and in arsenicinduced skin tumours [248]. Finally, miR-663 is a mediator of mitochondrial oxidative phosphorylation and has tumour suppressor functions, its promoter was found to be hypermethylated and its expression found to be decreased in arsenic skin cancer tissues compared to noncancerous control tissue [248].…”

Epigenetic and metabolic regulation of epidermal homeostasis

“… 116 Moreover, a recently discovered link between toxin‐induced promoter hypomethylation and mitochondrial biogenesis in skin cancer development further highlights the importance of coordinated epigenetic regulation and mitochondrial function. 117 When it comes to retrograde signalling, an increasing number of studies have identified potential alterations in the epigenetic landscape of the nuclear genome as a consequence of mitochondrial dysfunction. 114 For example, depletion of mtDNA results in significant changes in methylation pattern of a number of genes.…”

Recent Advances in Arsenic Research: Significance of Differential Susceptibility and Sustainable Strategies for Mitigation

“…However, mitochondrial DNA copy number was found to be significantly elevated among skin lesion individuals with increased expression of electron transport chain complex I, subunit ND6 and ND4 genes ( 93 ). Recently, we had reported about significant promoter hypomethylation with increased expression of mitochondrial biogenesis regulatory genes, Tfam and PGC1 α, among arsenic-induced skin lesion individuals compared to no skin lesion group, chronically exposed to arsenic through drinking water ( 94 ). Few studies also reported about altered promoter methylation of various important genes and subsequent change in gene expression among individuals with skin lesion compared to those without skin lesion explaining the vital role of epigenetic changes behind differential susceptibility ( Table 2 ).…”