Reduced nuclear DNA methylation and mitochondrial transcript changes in adenomas do not associate with mtDNA...

Area of Science:

• Genomics
• Cancer Biology
• Mitochondrial Biology

Background:

• Colorectal cancer (CRC) is characterized by altered mitochondrial function and nuclear DNA methylation.
• The role and occurrence of DNA methylation in the mitochondrial genome (mtDNA) within CRC remain unclear and controversial.
• Mitochondria contain a vital 16 kb circular genome essential for their function.

Purpose of the Study:

• To investigate the link between mitochondrial DNA methylation and mitochondrial gene transcription in colorectal adenomas.
• To evaluate the potential of mitochondrial DNA methylation as a biomarker for early-stage colorectal cancer.

Main Methods:

• RNA-sequencing and Whole Genome Bisulphite Sequencing (WGBS) were performed on mtDNA-enriched DNA.
• Samples included normal mucosa and paired adenoma tissues from patients.
• Analysis focused on transcriptional changes and methylation patterns in both nuclear and mitochondrial genomes.

Main Results:

• Adenomas exhibited reduced mitochondrial proton transport and decreased expression of three mtDNA-transcribed tRNAs compared to normal mucosa.
• Overall nuclear DNA methylation decreased in adenomas (68%) versus normal mucosa (75%).
• Mitochondrial DNA methylation was low (1%) in both normal and adenoma tissues, with methylation clusters found at ribosomal RNA genes, showing no significant difference between tissue types.

Conclusions:

• Low-level methylation exists at specific sites within the mitochondrial genome.
• This methylation is not associated with altered mitochondrial gene transcription in adenomas.
• Given the lack of large-scale changes, mitochondrial DNA methylation is unlikely to be a suitable biomarker for early-stage colorectal cancer.