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.
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Funding
This study was funded by National Key R&D Plan (No. 2017YFA0103202 and No. 2017YFA0103200), the Fundamental Research Funds for the Central Universities (2662017PY106, 2662016PY087, and 2662019YJ008) and Huazhong Agricultural University Startup funds to L.Z.
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Yi Yan, Lisheng Zhang—study concept and design; Yi Yan, Shichao Wang—acquisition of experimental data; Rui Wang, Puxuan Jiang, Yaqing Chen—assistance in molecular assays; Liang Zhang, Chenjiao Hou—assistance in cell experiment; Yi Yan—discussants, drafted manuscript; Lisheng Zhang—data organization and writing.
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Yi Yan, Shichao Wang, Rui Wang, Puxuan Jiang, Yaqing Chen, Liang Zhang, Chenjiao Hou, and Lisheng Zhang declares that they have no conflict of interest.
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Yan, Y., Wang, S., Wang, R. et al. Transcriptional regulation of microRNA-126a by farnesoid X receptor in vitro and in vivo. Biotechnol Lett 42, 1327–1336 (2020). https://doi.org/10.1007/s10529-020-02864-7
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DOI: https://doi.org/10.1007/s10529-020-02864-7