miR-29 Represses the Activities of DNA Methyltransferases and DNA Demethylases

International Journal of Molecular Sciences

Sumiyo Morita¹  Takuro Horii¹  Mika Kimura¹  Takahiro Ochiya²  Shoji Tajima³ 

[1] Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan; E-Mails:;Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; E-Mail:;Laboratory of Epigenetics, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan; E-Mail:

关键词: cancer;    DNA demethylation;    microRNA;    miR-29;    TDG;    TET1;   

DOI  :  10.3390/ijms140714647

来源: mdpi

【 摘 要 】

Members of the microRNA-29 (miR-29) family directly target the DNA methyltransferases, DNMT3A and DNMT3B. Disturbances in the expression levels of miR-29 have been linked to tumorigenesis and tumor aggressiveness. Members of the miR-29 family are currently thought to repress DNA methylation and suppress tumorigenesis by protecting against de novo methylation. Here, we report that members of the miR-29 family repress the activities of DNA methyltransferases and DNA demethylases, which have opposing roles in control of DNA methylation status. Members of the miR-29 family directly inhibited DNA methyltransferases and two major factors involved in DNA demethylation, namely tet methylcytosine dioxygenase 1 (TET1) and thymine DNA glycosylase (TDG). Overexpression of miR-29 upregulated the global DNA methylation level in some cancer cells and downregulated DNA methylation in other cancer cells, suggesting that miR-29 suppresses tumorigenesis by protecting against changes in the existing DNA methylation status rather than by preventing de novo methylation of DNA.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland