c-Myc modulates microRNA processing via the transcriptional regulation of Drosha

Sci Rep. 2013:3:1942. doi: 10.1038/srep01942.

Abstract

The c-Myc oncogenic transcription factor is known to regulate microRNA (miRNA) expression at the transcriptional level. However, little is known about the function of c-Myc in miRNA processing. Here, we report that Drosha, one of the most important components of the miRNA processing machinery, is a c-Myc target gene. c-Myc transactivates drosha mRNA expression, thus upregulating the Drosha protein level. A chromatin immunoprecipitation (ChIP) experiment revealed that c-Myc binds directly to the E-box of the drosha promoter. Both in vitro and in vivo microRNA processing assays demonstrated that c-Myc promotes miRNA processing by upregulating the Drosha expression level. Overall, our study reveals a previously unrecognised function of c-Myc in miRNA processing and provides valuable insight into a new aspect of how c-Myc regulates microRNA expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation*
  • Humans
  • Luciferases / metabolism
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / metabolism
  • MicroRNAs / genetics*
  • Promoter Regions, Genetic / genetics*
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribonuclease III / genetics*
  • Ribonuclease III / metabolism
  • Transcriptional Activation*
  • Tumor Cells, Cultured

Substances

  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Luciferases
  • DROSHA protein, human
  • Ribonuclease III