Document Detail


Hypoxia induces downregulation of soluble guanylyl cyclase β1 by miR-34c-5p.
MedLine Citation:
PMID:  23038777     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Soluble guanylyl cyclase (sGC) is the principal receptor for nitric oxide (NO) and crucial for the control of various physiological functions. The β1 subunit of sGC is obligatory for the biological stability and activity of the sGC heterodimer. MicroRNAs (miRNAs) are important regulators of gene expression and exert great influences on diverse biological activities. The aim of the present study was to determine whether or not the expression of sGCβ1 is specifically regulated by miRNAs. We report that miR-34c-5p directly targets sGCβ1 under hypoxia. Bioinformatics analysis of the sGCβ1 3'-untranslated region (3'-UTR) revealed a putative binding site for miR-34b-5p and miR-34c-5p, but only miR-34c-5p inhibited luciferase activity through interaction with sGCβ1 3'-UTR in HEK293T cells. Site-directed mutagenesis of the putative miR-34c-5p binding site abolished the negative regulation of luciferase expression. Overexpression of miR-34c-5p repressed the expression of sGCβ1 in stable cell lines, which was reversed by miR-34c-5p-specific sponge. Inoculation of mouse lung tissues in vitro with lentivirus bearing miR-34c-5p significantly decreased both the expression of sGCβ1 and NO-stimulated sGC activity, which was also rescued by miR-34c-5p-specific sponge. Furthermore, we identified the putative Sp1-binding site in the promoter region of miR-34c-5p. Luciferase reporter constructs revealed that Sp1 directly binds to the wild-type promoter of miR-34c-5p, which was confirmed by chromatin immunoprecipitation. In summary, these findings reveal that miR-34c-5p directly regulates sGCβ1 expression, and they identify the key transcription factor Sp1 that governs miR-34c-5p expression during hypoxia.
Authors:
Xiaojian Xu; Shumin Wang; Juan Liu; Dou Dou; Limei Liu; Zhengju Chen; Liping Ye; Huixia Liu; Qiong He; J Usha Raj; Yuansheng Gao
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-04
Journal Detail:
Title:  Journal of cell science     Volume:  125     ISSN:  1477-9137     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2013-02-28     Completed Date:  2014-01-29     Revised Date:  2014-07-02    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  6117-26     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
COS Cells
Cell Hypoxia / physiology*
Cells, Cultured
Cercopithecus aethiops
Down-Regulation
Female
Guanylate Cyclase / genetics,  metabolism*
HEK293 Cells
Humans
Mice
MicroRNAs / genetics,  metabolism*
Muscle, Smooth, Vascular / cytology
Protein Subunits
Random Allocation
Receptors, Cytoplasmic and Nuclear / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
HL059435/HL/NHLBI NIH HHS; HL075187/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/MIRN34 microRNA, human; 0/MicroRNAs; 0/Protein Subunits; 0/Receptors, Cytoplasmic and Nuclear; EC 4.6.1.2/Guanylate Cyclase; EC 4.6.1.2/soluble guanylyl cyclase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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