Niknam Maryam, Naghibalhossaini Fakhraddin, Hosseini Seyed Vahid, Zamani Mozhdeh, Mokarram Pooneh
Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Mol Biol Res Commun. 2025;14(4):307-316. doi: 10.22099/mbrc.2025.52486.2101.
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) ( and ) 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 were significantly higher in CRC tissues compared to normal ones. There was no significant relationship between the methylation of the genes and clinicopathological features of CRC patients. Interestingly, in most of the patients, the promoter hypermethylation of the , , and 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 , , and genes in CRC. Further large-scale studies will contribute to discovering the exact influences of methylation in CRC carcinogenesis and thereby may thereby provide novel targets and biomarkers for this lethal illness.
结直肠癌(CRC)死亡率高且发病率不断上升,是全球主要关注的问题。自噬途径在该疾病的致癌作用和耐药性中起着关键作用。表观遗传修饰是该途径的主要调控机制之一。本研究旨在调查启动子甲基化作为一种表观遗传修饰对伊朗南部21例CRC患者自噬相关基因(ATGs)(和)表达的影响。分别采用标准酚氯仿提取法和A BIOZOL RNA分离试剂盒提取组织DNA和RNA。分别使用甲基化特异性PCR和定量实时PCR方法确定所需基因的甲基化状态和转录水平。在大多数研究患者中,与正常组织相比,CRC组织中 的相对mRNA表达显著更高。 基因的甲基化与CRC患者的临床病理特征之间没有显著关系。有趣的是,在大多数患者中, 、 、 和 基因的启动子高甲基化导致其mRNA高表达。虽然启动子高甲基化通常会抑制基因表达,但癌症类型、阶段和补偿机制可能会逆转这种关联。这突出了CRC中 、 、 和 基因表观遗传调控的复杂性。进一步的大规模研究将有助于发现 甲基化在CRC致癌作用中的确切影响,从而可能为这种致命疾病提供新的靶点和生物标志物。