CRAT (Carnitine O-Acetyltransferase)

We generated a chemotherapy-resistant colorectal cancer cell line, HCT-15/DOX, via doxorubicin (DOX) induction...This research highlights notable differences in mitochondrial morphology and diverse mitochondrial metabolic functions between parental and DOX-resistant HCT-15 CRC cells. The findings of the present study provide insights into the mitochondrial metabolic changes associated with CRC chemotherapy resistance, offering valuable insights into the mechanisms underlying these changes and identifying potential therapeutic targets for addressing CRC chemotherapy resistance.

In the context of dyslipidemia conditions, MTDH is upregulated and suppresses the expression and activity of CrAT in RTECs, thereby inducing mitochondrial dysfunction and perturbing energy metabolism. These alterations exacerbate the injury to RTECs, consequently promoting the progression of DKD.

Mechanistically, we found that CRAT downregulation promoted OC growth and metastasis by increasing mitochondrial biogenesis to facilitate mitochondrial metabolism through reducing the acetylation of peroxisome proliferator-activated receptor-γ coactivator (PGC-1α). In summary, CRAT functions as a critical tumor suppressor in OC progression by enhancing PGC-1α-mediated mitochondrial biogenesis and metabolism, suggesting CRAT as a potential therapeutic target in treatment of OC.

Conclusions Our study constitutes the largest neoantigen dataset from integrated genome and transcriptome of CRC to date and illustrates the heterogeneity of the neoantigen landscape among CRC subtypes. The identified neoantigens may contribute to future individualized CRC immunotherapies.