miR-200b downregulates CFTR during hypoxia in human lung epithelial cells

Autor: Wojciech Kamysz, James F. Collawn, Zsuzsa Bebok, Jarosław Króliczewski, Rafal Bartoszewski, Sylwia Bartoszewska, Marek Sanak, Bogdan Jakiela
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
congenital
hereditary
and neonatal diseases and abnormalities
Transcription
Genetic
hsa-miR-200b-3p
Cystic Fibrosis Transmembrane Conductance Regulator
Down-Regulation
Biology
Biochemistry
Models
Biological
Cell Line
03 medical and health sciences
Downregulation and upregulation
In vivo
microRNA
medicine
Humans
RNA
Messenger
CFTR
lcsh:QH573-671
Molecular Biology
3' Untranslated Regions
Lung
Messenger RNA
Base Sequence
lcsh:Cytology
HIF-1
Epithelial Cells
micro-RNA 200b
Cell Biology
Hypoxia (medical)
respiratory system
Hypoxia-Inducible Factor 1
alpha Subunit
Molecular medicine
Epithelium
Cystic fibrosis transmembrane conductance regulator
Cell Hypoxia
Cell biology
respiratory tract diseases
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
biology.protein
medicine.symptom
5' Untranslated Regions
Research Article
Zdroj: Cellular & Molecular Biology Letters, Vol 22, Iss 1, Pp 1-14 (2017)
Cellular & Molecular Biology Letters
ISSN: 1689-1392
1425-8153
DOI: 10.1186/s11658-017-0054-0
Popis: Background Hypoxic conditions induce the expression of hypoxia-inducible factors (HIFs) that allow cells to adapt to the changing conditions and alter the expression of a number of genes including the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is a low abundance mRNA in airway epithelial cells even during normoxic conditions, but during hypoxia its mRNA expression decreases even further. Methods In the current studies, we examined the kinetics of hypoxia-induced changes in CFTR mRNA and protein levels in two human airway epithelial cell lines, Calu-3 and 16HBE14o-, and in normal primary bronchial epithelial cells. Our goal was to examine the posttranscriptional modifications that affected CFTR expression during hypoxia. We utilized in silico predictive protocols to establish potential miRNAs that could potentially regulate CFTR message stability and identified miR-200b as a candidate molecule. Results Analysis of each of the epithelial cell types during prolonged hypoxia revealed that CFTR expression decreased after 12 h during a time when miR-200b was continuously upregulated. Furthermore, manipulation of the miRNA levels during normoxia and hypoxia using miR-200b mimics and antagomirs decreased and increased CFTR mRNA levels, respectively, and thus established that miR-200b downregulates CFTR message levels during hypoxic conditions. Conclusion The data suggest that miR-200b may be a suitable target for modulating CFTR levels in vivo. Electronic supplementary material The online version of this article (10.1186/s11658-017-0054-0) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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