The methylation-expression correlation of autophagy-related genes in colorectal cancer patients from southern Iran

Document Type : Original article

Authors

1 Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

3 Colorectal Research center, Shiraz University of Medical Sciences, Shiraz, Iran

4 Autophagy Research Center, Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Colorectal cancer (CRC), which has high mortality and increasing morbidity is a major concern worldwide. The autophagy pathway plays a crucial role in carcinogenesis and drug resistance in this disease. Epigenetic modification is one of the main regulatory mechanisms for this pathway. This study aimed to investigate the impact of promoter methylation as one of the epigenetic modifications on the expression of autophagy-associated genes (ATGs) (ATG2B, ATG4D, ATG9A, and ATG9B) in 21 CRC patients from southern Iran. The tissue DNA and RNA were extracted by standard phenol-chloroform extraction method and A BIOZOL RNA isolation kit, respectively. The methylation status and transcript levels of desired genes were ascertained using the methylation-specific PCR and quantitative real-time PCR methods, respectively. In the majority of studied patients, the relative mRNA expressions of ATGs were significantly higher in CRC tissues compared to normal ones. There was no significant relationship between the methylation of the ATG genes and clinicopathological features of CRC patients. Interestingly, in most of the patients, the promoter hypermethylation of the ATG2B, ATG4D, ATG9A and ATG9B genes led to their high mRNA expression. Although promoter hypermethylation usually suppresses gene expression, the cancer type, stage, and compensatory mechanisms may reverse this association. This highlights the complexity of the epigenetic regulation of ATG2B, ATG4D, ATG9A and ATG9B genes in CRC. Further large-scale studies will contribute to discovering the exact influences of ATG methylation in CRC carcinogenesis and thereby may thereby provide novel targets and biomarkers for this lethal illness.

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