Department of Medical Laboratory Science, Rush University College of Health Sciences, Chicago, Illinois, USA.
Department of Gastroenterology, Rush University Medical Center, Chicago, Illinois, USA.
Int J Exp Pathol. 2022 Jun;103(3):74-82. doi: 10.1111/iep.12432. Epub 2022 Feb 28.
Dysregulation of DNA methylation patterns and non-coding RNA, including miRNAs, has been implicated in colon cancer, and these changes may occur early in the development of carcinoma. In this study, the role of epigenetics as early changes in colon tumorigenesis was examined through paired sample analysis of patient-matched normal, adenoma and carcinoma samples. Global methylation was assessed by genomic 5-methyl cytosine (5-mC) and long interspersed nuclear element-1 (LINE-1) promoter methylation by pyrosequencing. KRAS mutations were also assessed by pyrosequencing. Expression of miRNA, specifically, two microRNA genes-miR-200a and let-7c-was analysed using RT-qPCR. Differences in global methylation in adenomas were not observed, compared with normal tissue. However, LINE-1 methylation was decreased in adenomas (p = .056) and carcinomas (p = .011) compared with normal tissue. Expressions of miRNA, miR-200a and let-7c were significantly higher in adenomas than normal tissues (p = .008 and p = .045 respectively). Thus the significant changes in LINE-1 methylation and microRNA expression in precancerous lesions support an early role for epigenetic changes in the carcinogenic process. Epigenetic characteristics in adenomas may provide potential diagnostic and prognostic therapeutic targets early in cancer development at the adenoma stage.
DNA 甲基化模式和非编码 RNA（包括 miRNA）的失调与结肠癌有关，这些变化可能在癌前病变的早期就发生了。在这项研究中，通过对患者匹配的正常、腺瘤和癌组织的配对样本分析，研究了表观遗传学在结直肠肿瘤发生早期的作用。通过焦磷酸测序评估基因组 5-甲基胞嘧啶（5-mC）和长散布核元件-1（LINE-1）启动子的整体甲基化。还通过焦磷酸测序评估 KRAS 突变。使用 RT-qPCR 分析特定 miRNA 的表达，即两个 microRNA 基因 miR-200a 和 let-7c。与正常组织相比，腺瘤中没有观察到整体甲基化的差异。然而，与正常组织相比，LINE-1 甲基化在腺瘤（p =.056）和癌组织（p =.011）中减少。miRNA，miR-200a 和 let-7c 的表达在腺瘤中明显高于正常组织（p =.008 和 p =.045 分别）。因此，癌前病变中 LINE-1 甲基化和 microRNA 表达的显著变化支持表观遗传变化在致癌过程中早期发挥作用。腺瘤中的表观遗传特征可能为癌症发展早期的腺瘤阶段提供潜在的诊断和预后治疗靶点。
