Transcriptional regulation of microRNA-126a by farnesoid X receptor in vitro and in vivo.

Objectives: Recent research has indicated the microRNA-126a (miR-126a) is an endothelial cell-specific and highly conserved endogenous small non-coding RNA molecule. It contributes to the vascular integrity and angiogenesis, but the molecular regulation mechanism of miR-126a remains unknown.

Results: Herein, quantitative real-time polymerase chain reaction (qRT-PCR) results showed that Farnesoid X Receptor (FXR) activation promoted miR-126a expression in HepG2, LO2, and Hep1-6 cells. Furthermore, FXR was found to transcriptionally regulate the miR-126a by binding to its DR8 site. The binding site of FXR was confirmed on intron 6 or 7 of miR-126a host gene epidermal growth factor-like domain 7 (EGFL7) by luciferase reporter assays, electrophoretic mobility shift assays (EMSAs) and chromatin immunoprecipitation (ChIP) assays.

Conclusions: All these data collectively suggest that FXR regulates transcripts of miR-126a by binding to DR8 in miR-126a gene promoter. This study may provide a molecular therapeutic target for angiogenic disorders, aging, and liver failure.