MicroRNA-433 Inhibits the Proliferation and Migration of HUVECs and Neurons by Targeting Hypoxia-Inducible Factor 1 Alpha.
Emerging evidence has demonstrated an important role of microRNAs (miRNAs) in the pathogenesis of cerebral infarction. In the present study, a down-regulation of microRNA-433 (miR-433) is identified in hypoxia-induced human umbilical vein vascular endothelial cells (HUVECs) as well as in rat neurons, and is found to be negatively regulated cell proliferation and migration. Moreover, the expression of miR-433 is inversely correlated with the expression of hypoxia-inducible factor 1 alpha (HIF-1α), which has been shown to play critical role in responding to hypoxia conditions. Overexpression or knockdown of miR-433 responsively alters both mRNA and protein levels of HIF-1α and its downstream genes, vascular endothelial growth factor, Glut-1, and Angpt2. In a luciferase reporter system, miR-433 down-regulates the luciferase activity of HIF-1α 3'-UTR, and these effects are abolished by a mutation in the putative miR-433-binding site. Further investigation confirms that knockdown of HIF-1α blocked the stimulatory effect of anti-miR-433, while overexpression of HIF-1α reversed the inhibitory effects of pre-miR-433 on proliferation and migration of HUVEC and neurons. Taken together, our findings indicate that miR-433 plays an important role in response to hypoxia, inhibiting HUVEC and neuron proliferation and migration by down-regulating HIF-1α.
Institute of neurobiology, Xi'an Jiaotong Univerisity Health Science Center, No. 76 West Yanta street, Xi'an, 710061, China.|Department of Neurology, Xi'an Central Hospital, Xi'an, 710003, China.
Lin
L
Zhang
Department of Neurology, Xi'an Central Hospital, Xi'an, 710003, China.
Yuanxiao
Y
Zhang
Institute of neurobiology, Xi'an Jiaotong Univerisity Health Science Center, No. 76 West Yanta street, Xi'an, 710061, China.
Xiaohua
X
Zhang
School of Pharmaceutical Sciences, Xi'an Medical University, Xi'an, 710021, China.
Yan
Y
Zhang
Department of Neurology, Xi'an Central Hospital, Xi'an, 710003, China.
Yi
Y
Jiang
Institute of neurobiology, Xi'an Jiaotong Univerisity Health Science Center, No. 76 West Yanta street, Xi'an, 710061, China.
Xinli
X
Xiao
Department of Anesthesia, The first Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710061, China.
Jing
J
Tan
Department of Cardiology, Xi'an North Hospital, Xi'an, 710043, China.
Wei
W
Yuan
Institute of neurobiology, Xi'an Jiaotong Univerisity Health Science Center, No. 76 West Yanta street, Xi'an, 710061, China. yongliucb@163.com.
Yong
Y
Liu
D020413:3' Untranslated Regions; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D020413:3' Untranslated Regions; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C548883:MIRN433 microRNA, human; D035683:MicroRNAs
HUVEC; Hypoxia; Hypoxia-inducible factor 1 alpha; MicroRNA-433; Neuron