Change search
ReferencesLink to record
Permanent link

Direct link
MicroRNA-519c suppresses hypoxia-inducible factor-1alpha expression and tumor angiogenesis.
Show others and affiliations
2010 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 70, no 7, 2675-85 p.Article in journal (Refereed) Published
Abstract [en]

Hypoxia-inducible factor-1alpha (HIF-1alpha) is widely considered to be one of the key regulators of tumor angiogenesis. The upstream regulation is complex and involves several growth factors, cytokines, and hypoxia. Herein, we have identified miR-519c as a hypoxia-independent regulator of HIF-1alpha, acting through direct binding to the HIF-1alpha 3' untranslated region and leading to reduced tumor angiogenesis. Overexpression of miR-519c resulted in a significant decrease of HIF-1alpha protein levels and reduced the tube formation of human umbilical vein endothelial cells; similarly, antagomir inhibition of miR-519c increased the level of HIF-1alpha protein and enhanced angiogenic activity, suggesting an important role of miR-519c in HIF-1alpha-mediated angiogenesis. Consistent with the overexpression of miR-519c in cancer patients with better prognosis, mice injected with miR-519c-overexpressing cells exhibited dramatically reduced HIF-1alpha levels, followed by suppressed tumor angiogenesis, growth, and metastasis. In addition, we found that hepatocyte growth factor (HGF), a known HIF-1alpha inducer, reduced the miR-519c levels through an Akt-dependent pathway. This regulation was posttranscriptional and may be mediated by suppression of miR-519c maturation. Taken together, our findings provide the first evidence that miR-519c is a pivotal regulator of tumor angiogenesis and that microenvironmental HGF contributes to regulating miR-519c biogenesis in cancer cells.

Place, publisher, year, edition, pages
2010. Vol. 70, no 7, 2675-85 p.
National Category
Cell Biology
URN: urn:nbn:se:umu:diva-106966DOI: 10.1158/0008-5472.CAN-09-2448PubMedID: 20233879OAI: diva2:845815
Available from: 2015-08-13 Created: 2015-08-13 Last updated: 2015-08-13

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
In the same journal
Cancer Research
Cell Biology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 18 hits
ReferencesLink to record
Permanent link

Direct link