Mitochondrial Complex I Molecular Alterations in Sapajus apella as a Human Gastric Carcinogenesis Model After MNU Exposure

TL;DR

This study explores mitochondrial gene changes in a monkey model to understand how they contribute to gastric cancer development.

Contribution

The study identifies specific mitochondrial gene alterations linked to gastric cancer progression in an animal model.

Findings

Two synonymous alterations were found in the ND1 gene.

A non-synonymous alteration in ND3 may reduce Complex I efficiency and increase reactive oxygen species.

ND1 and ND3 alterations were observed in highly aggressive cancer cell lines.

Abstract

Gastric cancer (GC) remains among the top five global health problems. Therefore, comprehending the tumor energetic behavior is critical to understanding its progression. This study aimed to investigate mitochondrial DNA (mtDNA) alterations in GC cancer cell lines in an animal model.

Four mitochondrial genes (COI, ATP8, ND1, and ND3) were analyzed in GC (AGP01, ACP02, ACP03, and PG100) and control (Walker 256 carcinosarcoma) cell lines inoculated in
Sapajus apella
, exposed and not exposed to N‐methyl‐N‐nitrosourea.

Two synonymous alterations were identified in ND1. In ND3, a non‐synonymous alteration (A10398G ➔ Thr114Ala) may decrease the respiratory chain Complex I efficiency, enhancing cellular reactive oxygen species and contributing to mtDNA damage. As alterations in ND1 and ND3 were observed in highly aggressive cell lines, our results suggest these genes may play crucial roles in energetic efficiency and gastric carcinogenesis.

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