表观遗传修饰与环状RNA在结直肠癌中相互作用的研究进展

Crosstalk between epigenetic modification and circRNA in colorectal cancer:recent advances

结直肠癌(colorectal cancer,CRC)是全球第三大常见的恶性肿瘤,目前针对该病的诊断和治疗方法都存在局限性。既往的研究表明,表观遗传修饰在结直肠癌的进展中发挥了重要作用。表观遗传修饰是指基因功能在DNA序列不变的情况下发生了可遗传的变化,导致相似DNA的细胞最终发育成具有不同功能的细胞,其中主要包括DNA/RNA甲基化修饰、组蛋白修饰、非编码RNA转录后调控等。环状RNA(circular RNA,circRNA)是非编码RNA中的一种具有稳定环状结构的RNA分子,广泛存在于多种细胞中,且可以通过多种通路影响肿瘤的进展。目前许多研究表明表观遗传修饰可以影响circRNA的生物学功能,而circRNA也能通过靶向表观遗传修饰相关分子参与结直肠癌的进展。其中,研究发现一方面N^(6)-甲基腺苷(N^(6)-methyladenosine,m^(6)A)可以直接影响circRNA的生成、翻译及功能,另一方面circRNA也可以调控m^(6)A修饰及其调节因子,从而影响疾病的发生发展及转移。DNA甲基化和组蛋白修饰也与circRNA有潜在的相互作用。该文描述了表观遗传修饰与circRNA在结直肠癌中的相互作用,以及它们在癌症发展中的作用,并提出了它们在诊断与治疗中的潜在应用和未来研究方向。

Colorectal cancer(CRC)is generally regarded as the third frequent malignancy worldwide,while current diagnosis and treatment of the disease are limited.The previous studies of CRC revealed that epigenetic modification plays a crucial role in the progression of CRC.Epigenetic modification is identified as heritable changes in gene functions that occur without changing the DNA sequence,resulting in cells with similar DNA eventually developing into different types with different functions,which encompasses DNA/RNA methylation,histone modification,and non-coding RNA regulation.Circular RNA(circRNA),a kind of non-coding RNA that forms a covalently closed loop,is widely present in various cells which drive initiation and progression of cancers through multiple pathways.The emerging data show that epigenetic modification may affect the biological functions of circRNA,while circRNA can also participate in the progression of CRC by targeting molecules related to epigenetic modification.N^(6)-methyladenosine(m^(6)A)has been found to directly promote production,translation,and functions of circRNA on the one hand,and interact with circRNA on the other hand,thereby altering onset,progression,and metastasis of the disease.DNA methylation and histone modification have also been observed to have potential interaction with circRNA.This review provides a brief overview about the association between current epigenetic modifications and circRNA,and the significant role they may play in the progression of CRC,and also outlines the potential applications to diagnosis and treatment,and the research direction in the future.