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Up-regulation of FGFBP1 signaling contributes to miR-146a-induced angiogenesis in human umbilical vein endothelial cells.


ABSTRACT: Recent microRNA expression profiling studies have documented an up-regulation of miR-146a in several angiogenesis models. However, the underlying molecular mechanism of miR-146a in the angiogenic activity of endothelial cells has not been clearly elucidated. The present study was aimed to evaluate whether miR-146a promotes angiogenesis in HUVECs by increasing FGFBP1 expression via directly targeting CREB3L1. miR-146a was over expressed in HUVECs via lentiviral-miR-146a. Expression profiling analysis found miR-146a over expression resulted in up-regulation of angiogenesis and cytokine activity associated genes including FGF2. Further a combination of bioinformatics and experimental analyses demonstrated the CREB3L1 as a bona fide functional target of miR-146a during angiogenesis. Moreover, CREB3L1 inhibited luciferase expression from FGFBP1 promoter containing only CRE elements. Furthermore, CREB3L1 inhibited FGFBP1 expression by binding to two CRE-like sites located at approximately -1780-1777 and -868-865?bp relative to the FGFBP1 transcription start site. Additionally, ectopic expression of CREB3L1 decreased miR-146a-induced FGF2 secretion. These findings indicate that the miR-146a-CREB3L1-FGFBP1 signaling axis plays an important role in the regulation of angiogenesis in HUVECs and provides a potential therapeutic target for anti-angiogenic therapeutics.

SUBMITTER: Zhu HY 

PROVIDER: S-EPMC4848533 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Up-regulation of FGFBP1 signaling contributes to miR-146a-induced angiogenesis in human umbilical vein endothelial cells.

Zhu Hua-Yu HY   Bai Wen-Dong WD   Liu Jia-Qi JQ   Zheng Zhao Z   Guan Hao H   Zhou Qin Q   Su Lin-Lin LL   Xie Song-Tao ST   Wang Yun-Chuan YC   Li Jun J   Li Na N   Zhang Yi-Jie YJ   Wang Hong-Tao HT   Hu Da-Hai DH  

Scientific reports 20160428


Recent microRNA expression profiling studies have documented an up-regulation of miR-146a in several angiogenesis models. However, the underlying molecular mechanism of miR-146a in the angiogenic activity of endothelial cells has not been clearly elucidated. The present study was aimed to evaluate whether miR-146a promotes angiogenesis in HUVECs by increasing FGFBP1 expression via directly targeting CREB3L1. miR-146a was over expressed in HUVECs via lentiviral-miR-146a. Expression profiling anal  ...[more]

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