MicroRNA-143 is downregulated in breast cancer and regulates DNA methyltransferases 3A in breast cancer cells

Tumour Biol. 2014 Mar;35(3):2591-8. doi: 10.1007/s13277-013-1341-7. Epub 2013 Nov 13.

Abstract

MicroRNAs (miRNAs) are small non-protein-coding RNAs that regulate expression of a wide variety of genes including those involved in cancer development. Here, we investigate the role of miR-143 in breast cancer. In this study, we showed that miR-143 was frequently downregulated in 80% of breast carcinoma tissues compared to their adjacent noncancerous tissues. Ectopic expression of miR-143 inhibited proliferation and soft agar colony formation of breast cancer cells and also downregulated DNA methyltransferase 3A (DNMT3A) expression on both mRNA and protein levels. Restoration of miR-143 expression in breast cancer cells reduces PTEN hypermethylation and increases TNFRSF10C methylation. DNMT3A was demonstrated to be a direct target of miR-143 by luciferase reporter assay. Furthermore, miR-143 expression was observed to be inversely correlated with DNMT3A mRNA and protein expression in breast cancer tissues. Our findings suggest that miR-143 regulates DNMT3A in breast cancer cells. These findings elucidated a tumor-suppressive role of miR-143 in epigenetic aberration of breast cancer, providing a potential development of miRNA-based treatment for breast cancer.

MeSH terms

  • Blotting, Western
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA (Cytosine-5-)-Methyltransferases / biosynthesis*
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA Methylation / physiology
  • Down-Regulation
  • Epigenesis, Genetic / physiology
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • MicroRNAs / biosynthesis*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

Substances

  • MIRN143 microRNA, human
  • MicroRNAs
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA methyltransferase 3A