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

  • Biotechnol Lett. 2020 Aug;42(8):1327-1336. doi: 10.1007/s10529-020-02864-7.
Yi Yan  1 ,  Shichao Wang  1 ,  Rui Wang  1 ,  Puxuan Jiang  1 ,  Yaqing Chen  1 ,  Liang Zhang  1 ,  Chenjiao Hou  1 ,  Lisheng Zhang  2
Affiliations
  • 1. College of Veterinary Medicine, Bio-medical Center, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
  • 2. College of Veterinary Medicine, Bio-medical Center, Huazhong Agricultural University, Wuhan, Hubei, 430070, China. [email protected].
PMID: 32221722 DOI: 10.1007/s10529-020-02864-7
Abstract

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.

Keywords
Farnesoid X receptor; Promoter; Transcription; microRNA-126a.
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