DNA methylation regulates MicroRNA expression

Cancer Biol Ther. 2007 Aug;6(8):1284-8. doi: 10.4161/cbt.6.8.4486. Epub 2007 May 24.

Abstract

MicroRNAs (miRNAs), an important class of small regulatory molecules for gene expression, are transcribed by RNA polymerase II. But little is known about the mechanisms that control miRNA expression. Comparing miRNA expression profiles between colon cancer cell line HCT 116 and its derivative, DNA methyltransferase 1 and 3b (DNMT1 and DNMT3b) double knockout cell line, we found that the expression of about 10% miRNAs was regulated by DNA methylation. In addition, neither 5-aza-2'-deoxycytidine treatment nor deletion of DNMT1 alone recapitulated miRNA expression profile seen in the double knockout cell line, suggesting that miRNA expression was tightly controlled by DNA methylation and partial methylation reduction was not sufficient for miRNA reexpression. We also found that HOXA3 and HOXD10 were putative targets of mir-10a, one of the differentially expressed miRNAs that is located in HOX gene cluster.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Line, Tumor
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism
  • CpG Islands / genetics
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation*
  • Gene Expression Regulation, Neoplastic*
  • Homeodomain Proteins / genetics
  • Humans
  • MicroRNAs / metabolism*
  • Transcription Factors / genetics

Substances

  • HOXA3 protein, human
  • Homeodomain Proteins
  • MicroRNAs
  • Transcription Factors
  • HOXD10 protein, human
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA methyltransferase 3B
  • DNMT1 protein, human