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Regulation of HIF-1alpha and VEGF by miR-20b tunes tumor cells to adapt to the alteration of oxygen concentration
Regulation of HIF-1alpha and VEGF by miR-20b tunes tumor cells to adapt to the alteration of oxygen concentration
- Source :
- PLoS ONE, PLoS ONE, Vol 4, Iss 10, p e7629 (2009)
- Publication Year :
- 2009
-
Abstract
- The regulation of HIF-1alpha is considered to be realized by pVHL-mediated ubiquitin-26S proteasome pathway at a post-transcriptional level. The discovery of a class of small noncoding RNAs, called microRNAs, implies alternative mechanism of regulation of HIF-1alpha. Here, we show that miR-20b plays an important role in fine-tuning the adaptation of tumor cells to oxygen concentration. The inhibition of miR-20b increased the protein levels of HIF-1alpha and VEGF in normoxic tumor cells; the increase of miR-20b in hypoxic tumor cells, nevertheless, decreased the protein levels of HIF-1alpha and VEGF. By using luciferase reporter vector system, we confirmed that miR-20b directly targeted the 3'UTR of Hif1a and Vegfa. On the other hand, the forced overexpression of HIF-1alpha in normoxic tumor cells downregulated miR-20b expression. However, HIF-1alpha knockdown in hypoxic tumor cells caused the increase of miR-20b. The differential expression of miR-20b has important biological significance in tumor cells, either enhancing the growth or favoring the survival of tumor cells upon the oxygen supply. Thus, we identify a novel molecular regulation mechanism through which miR-20b regulates HIF-1alpha and VEGF and is regulated by HIF-1alpha so to keep tumor cells adapting to different oxygen concentrations.
- Subjects :
- Vascular Endothelial Growth Factor A
Gastroenterology and Hepatology/Gastrointestinal Cancers
Genetic Vectors
lcsh:Medicine
Biology
Mice
Cell Line, Tumor
Neoplasms
Molecular Biology/Translational Regulation
Gene expression
microRNA
medicine
Animals
Humans
lcsh:Science
Hypoxia
Cell Biology/Gene Expression
Gene knockdown
Mice, Inbred BALB C
Multidisciplinary
lcsh:R
Transfection
Cell Biology/Cellular Death and Stress Responses
Hypoxia (medical)
Hypoxia-Inducible Factor 1, alpha Subunit
Molecular biology
Cell biology
Gene Expression Regulation, Neoplastic
Oxygen
Vascular endothelial growth factor A
MicroRNAs
HIF1A
Oncology
Apoptosis
lcsh:Q
medicine.symptom
Neoplasm Transplantation
Research Article
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 4
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....db807a12595c0e4f7bcd501987f942bf