Norollahi Seyedeh Elham, Foumani Maryam Gholamniya, Pishkhan Maryam Khoshbakht, Shafaghi Afshin, Alipour Majid, Jamkhaneh Vida Baloui, Marghoob Mohammad Namayan, Vahidi Sogand
Cancer Research Center and Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran.
School of Nursing and Midwifery, Guilan University of Medical Sciences, Rasht, Iran.
Oman Med J. 2021 Nov 10;36(6):e315. doi: 10.5001/omj.2020.93. eCollection 2021 Nov.
Epigenetic modifications, particularly DNA methylation, is commonplace and a remarkable factor in carcinogenesis transformation. Conspicuously, previous findings have presented a cluster of irregular promoter methylation alterations related with silencing of tumor suppressor genes, little is accepted regarding their sequential DNA methylation (hypo and hyper) modifications during the cancer progression. In this way, fluctuations of DNA methylation of many genes, especially MYC, SMAD2/3, and DNMT3A, have an impressive central key role in many different cancers, including colorectal cancer (CRC). CRC is distinguished by DNA methylation, which is related to tumorigenesis and also genomic instability. Importantly, molecular heterogeneity between multiple adenomas in different patients with CRC may show diverse developmental phenotypes for these kinds of tumors. Conclusively, studying factors that are involved in CRC carcinogenesis, especially the alterations in epigenetic elements, such as DNA methylation besides RNA remodeling, and histone modification, acetylation and phosphorylation, can be influential to find new therapeutic and diagnostic biomarkers in this type of malignancy. In this account, we discuss and address the potential significant methylated modifications of these genes and their importance during the development of CRC carcinogenesis.
表观遗传修饰,尤其是DNA甲基化,在癌症发生转化过程中很常见且是一个重要因素。值得注意的是,先前的研究发现了一系列与肿瘤抑制基因沉默相关的不规则启动子甲基化改变,但对于它们在癌症进展过程中的顺序性DNA甲基化(低甲基化和高甲基化)修饰了解甚少。如此一来,许多基因的DNA甲基化波动,尤其是MYC、SMAD2/3和DNMT3A,在包括结直肠癌(CRC)在内的许多不同癌症中都起着至关重要的核心作用。CRC以DNA甲基化为特征,这与肿瘤发生以及基因组不稳定性有关。重要的是,不同CRC患者多个腺瘤之间的分子异质性可能表现出这类肿瘤多样的发育表型。总之,研究参与CRC致癌过程的因素,尤其是表观遗传元件的改变,如除RNA重塑外的DNA甲基化以及组蛋白修饰、乙酰化和磷酸化,可能有助于在这类恶性肿瘤中找到新的治疗和诊断生物标志物。在此,我们讨论并阐述这些基因潜在的重要甲基化修饰及其在CRC致癌过程中的重要性。