Abstract
Mitochondrial DNA (mtDNA) has been identified as a significant genetic biomarker in disease, cancer and evolution. Mitochondria function as modulators for regulating cellular metabolism. In the clinic, mtDNA variations (mutations/single nucleotide polymorphisms) and dysregulation of mitochondria-encoded genes are associated with survival outcomes among cancer patients. On the other hand, nuclear-encoded genes have been found to regulate mitochondria-encoded gene expression, in turn regulating mitochondrial homeostasis. These observations suggest that the crosstalk between the nuclear genome and mitochondrial genome is important for cellular function. Therefore, this review summarizes the significant mechanisms and functional roles of mtDNA variations (DNA level) and mtDNA-encoded genes (RNA and protein levels) in cancers and discusses new mechanisms of crosstalk between mtDNA and the nuclear genome.
Highlights
The sequence of the mitochondrial genome was first identified in 1981 [1]
Functional and clinical studies have reported that mitochondrial DNA mutations, Mitochondrial DNA (mtDNA) single-nucleotide polymorphisms (SNPs), mtDNA-encoded microRNAs, mitochondria-derived long noncoding RNAs and mitochondrial proteins are involved in cancer progression (Figure 1)
Mitochondrial homeostasis has become an important event for cancer progression
Summary
The sequence of the mitochondrial genome was first identified in 1981 [1]. Mitochondria contain distinct cell membranes and their own genome (circular DNA), which encode. Functional and clinical studies have reported that mitochondrial DNA (mtDNA) mutations, mtDNA single-nucleotide polymorphisms (SNPs), mtDNA-encoded microRNAs (mitomiRs), mitochondria-derived long noncoding RNAs (lncRNAs) and mitochondrial proteins are involved in cancer progression (Figure 1). Alterations in nuclear DNA-encoded genes lead to an imbalance in mitochondrial homeostasis, suggesting that crosstalk between the nuclear and mitochondrial genomes is important in cancer biology. Taken together, these findings suggest that mitochondria-related molecule (DNA, RNA and protein) is crucial for several important physiological homeostasis and cancer progression. This review summarizes the functions and clinical relevance of the mitochondrial DNA (DNA level), mitochondria-encoded ncRNA (RNA level) and proteins (protein level) in cancer progression and discusses new mechanisms of crosstalk between mtDNA and the nuclear genome. D: tRNA Asp, K: tRNA Lys, G: tRNA Gly, R: tRNA Arg, H: tRNA His, S: tRNA Ser, L: tRNA Leu, E: tRNA Glu, T: tRNA Thr and P: tRNA Pro
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