miR-381 suppresses C/EBPα-dependent Cx43 expression in breast cancer cells

Biosci Rep. 2015 Oct 8;35(6):e00266. doi: 10.1042/BSR20150167.


Cx43 (connexin43) is an enhancer of the metastasis of breast cancer cells. Our previous study identified miR-381 as an indirect suppressor of Cx43 gene expression, with the precise mechanism being not understood. In the present study, using a reporter gene assay, we found that miR-381 suppressed Cx43 gene expression via the promoter region -500/-250. With site-directed gene mutation, we demonstrated that miR-381 could directly bind with the sequences CACUUGUAU in the 3'-UTR so as to inhibit C/EBPα (CCAAT/enhancer-binding protein α) expression. C/EBPα was further identified as a novel transcription factor by binding to a canonic element (AATTGTC) locating at -459/-453 in the promoter region of the Cx43 gene. Functionally, we demonstrated that miR-381 suppressed C/EBPα- and Cx43-dependent migration and invasion of breast cancer cells. Finally, we revealed that decreased levels of miR-381 as well as increased expression of C/EBPα and Cx43 in the metastatic breast cancer cells and tissues. Therefore we are the first to identify that miR-381 suppresses C/EBPα-dependent Cx43 expression in breast cancer cells. The miR-381-C/EBPα-Cx43 axis might be a useful diagnostic and therapeutic target of metastatic breast cancer.

Keywords: 3′-UTR; C/EBPα; Cx43; MCF-7; MDA-MB-231; miR-381.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • CCAAT-Enhancer-Binding Proteins / biosynthesis*
  • CCAAT-Enhancer-Binding Proteins / genetics
  • Cell Line, Tumor
  • Connexin 43 / biosynthesis*
  • Connexin 43 / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Metastasis
  • Promoter Regions, Genetic


  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • Connexin 43
  • MIRN381 microRNA, human
  • MicroRNAs