대한신장학회

논문분류	춘계학술대회 초록집
제목	Comprehensive Regulatory MicroRNAs that Govern Epigenetic Machinery in Cancer
저자	*Suk woo NAM
출판정보	2017; 2017(1):
키워드
초록	MicroRNAs (miRNAs) comprise species of short noncoding RNA that regulate gene expression post-transcriptionally. Recently, it was also found that miRNAs as tumor suppressor genes or oncogenes affect cancer development by inhibiting the expressions of proteins that regulate cellular activities, and that miRNAs play important roles in the initiation of cancer. According to miRNA target databases, one miRNA may regulate many genes as its targets, while one gene may be targeted by many miRNAs. It has also been reported that multiple or a cluster of miRNAs co-operatively regulate a gene, which is related to carcinogenesis. However, numerous studies revealed a one-to-one relationship between miRNA and its target gene. On the other hand, recent studies showed that one miRNA could regulate many genes as its targets, while one gene could be targeted by many miRNAs. Recent studies have demonstrated that epigenetic mechanisms, including DNA methylation and histone modification, not only regulate the expression of protein-encoding genes, but also miRNAs. Conversely, another subset of miRNAs controls the expression of important epigenetic regulators, including DNA methyltransferases, histone deacetylases and polycomb group genes. This complicated network of feedback between miRNAs and epigenetic pathways appears to form an epigenetics-miRNA regulatory circuit, and to organize the whole gene expression profile. When this regulatory circuit is disrupted, normal physiological functions are interfered with, contributing to various disease processes. The concept of miRNA targeting of “one for many or all” led us to conceive a hypothesis that a single miRNA may govern comprehensive epigenetic effector genes related to cancer, and silencing of this miRNA can cause excessive deregulation of oncogenic epigenetic modifiers. In the present study, we demonstrated that at least 10 potent oncogenic epigenetic modifiers were significantly overexpressed in gastric cancer through hypermethylation of miR-495-3p gene promoter region and that miR-495-3p has a pivotal role in maintaining the activity of these 10 genes in normal gastric cell homeostasis. These results imply that miR-495-3p functions as a potent tumor suppressor by governing multiple oncogenic epigenetic modifiers in gastric carcinogenesis, and suggest that miR-495-3p has a potential therapeutic value in the treatment of gastric cancer.
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