microRNA regulation of expression of the cystic fibrosis transmembrane conductance regulator gene

Austin E. Gillen, Nehal Gosalia, Shih Hsing Leir, Ann Harris*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


The CFTR (cystic fibrosis transmembrane conductance regulator) gene shows a complex temporal and spatial pattern of expression that is controlled by multiple cis-acting elements interacting with the basal promoter. Although significant progress has been made towards understanding these genomic elements, there have been no reports of post-transcriptional regulation of CFTR by miRNAs (microRNAs). In the present study, we identify two miRNAs, hsa-miR-145 and hsa-miR-494, which regulate CFTR expression by directly targeting discrete sites in the CFTR 3′ UTR (untranslated region). We show that at least 12 miRNAs are capable of repressing endogenous CFTR mRNA expression in the Caco-2 cell line. Ten of these also inhibit expression of a reporter construct containing the CFTR 3′ UTR in one or more cell lines, and five repress endogenous CFTR protein expression in Caco-2 cells. Moreover, at least three are expressed in primary human airway epithelial cells, where CFTR expression is maintained at low levels in comparison with intestinal cell lines. Three of the miRNAs that target CFTR, hsa-miR-384, hsa-miR-494 and hsamiR-1246, also inhibit expression of a reporter carrying the Na + - K + -Cl - co-transporter SLC12A2 [solute carrier family 12 (Na + - K + -Cl - transporters), member 2] 3′ UTR, suggesting that these miRNAs may play a more general role in regulating chloride transport in epithelial cells.

Original languageEnglish (US)
Pages (from-to)25-32
Number of pages8
JournalBiochemical Journal
Issue number1
StatePublished - Aug 15 2011


  • Cystic fibrosis transmembrane conductance regulator (CFTR)
  • Member 2 (SLC12A2)
  • Post-transcriptional regulation
  • Solute carrier family 12 (Na -K -Cl transporters)
  • microRNA (miRNA)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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