Silencing of miR-1-1 and miR-133a-2 cluster expression by DNA hypermethylation in colorectal cancer

Oncol Rep. 2012 Sep;28(3):1069-76. doi: 10.3892/or.2012.1899. Epub 2012 Jul 5.


MicroRNAs are small non-coding RNA molecules that play important roles in the multistep process of colorectal carcinoma (CRC) development. The present study evaluated the relationship between miR-1-1 and miR-133a-2 expression and DNA methylation, and its putative biological role in CRC. The results indicated that DNA methylation regulated the expression of the miR-1-1 and miR-133a-2 cluster in CRC cell lines. Expression of miR-1 and miR-133a was further evaluated in 64 paired tissue samples (CRC tumor and adjacent normal mucosa) using the stem-loop real-time polymerase chain reaction. The miR-1-133a cluster displayed significantly lower expression in CRC tissue compared to adjacent normal mucosa (P<0.001). The results also indicated frequent hypermethylation of the CpG islands upstream of miR-1-133a (54.6%). Liver metastatic tissues exhibited significantly lower miR-1 (P<0.001) and miR-133a (P<0.001) expression compared to adjacent normal mucosa. Expression of the miR-1-133a cluster inversely correlated with TAGLN2 in the tumor specimens. In conclusion, epigenetic repression of the miR-1-133a cluster may play a critical role in colorectal cancer metastasis by silencing TAGLN2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Carcinoma / secondary
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • CpG Islands
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • DNA Methylation*
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing*
  • Humans
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / secondary
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Multigene Family
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Transcription, Genetic


  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • LASP1 protein, human
  • LIM Domain Proteins
  • MIRN1 microRNA, human
  • MIRN133 microRNA, human
  • MicroRNAs
  • Microfilament Proteins
  • Muscle Proteins
  • transgelin