Scientific reports, 2015-07, Vol.5 (1), p.12495-12495, Article 12495
2015
Details
- Autor(en) / Beteiligte
- Titel
- Hypoxia-inducible miR-182 enhances HIF1α signaling via targeting PHD2 and FIH1 in prostate cancer
- Ist Teil von
- Scientific reports, 2015-07, Vol.5 (1), p.12495-12495, Article 12495
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2015
- Link zum Volltext
- Quelle
- EZB-FREE-00999 freely available EZB journals
- Beschreibungen/Notizen
- Activation of hypoxia-inducible factor 1α (HIF1α) controls the transcription of genes governing angiogenesis under hypoxic condition during tumorigenesis. Here we show that hypoxia-responsive miR-182 is regulated by HIF1α at transcriptional level. Prolyl hydroxylase domain enzymes (PHD) and factor inhibiting HIF-1 (FIH1), negative regulators of HIF1 signaling, are direct targets of miR-182. Overexpression of miR-182 in prostate cancer cells led to a reduction of PHD2 and FIH1 expression and an increase in HIF1α level either under normoxic or hypoxic condition. Consistently, inhibition of miR-182 could increase PHD2 and FIH1 levels, thereby reducing the hypoxia-induced HIF1α expression. Matrigel plug assay showed that angiogenesis was increased by miR-182 overexpression, and vice versa. miR-182 overexpression in PC-3 prostate cancer xenografts decreased PHD2 and FIH1 expression, elevated HIF1α protein levels, and increased tumor size. Lastly, we revealed that the levels of both miR-182 and HIF1α were elevated, while the expression PHD2 and FIH1 was downregulated in a mouse model of prostate cancer. Together, our results suggest that the interplay between miR-182 and HIF1α could result in a sustained activation of HIF1α pathway, which might facilitate tumor cell adaption to hypoxic stress during prostate tumor progression.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/srep12495Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4513346
- Format
- –
- Schlagworte
- Animals, Cell Hypoxia - genetics, Cell Line, Tumor, Heterografts, Hypoxia-Inducible Factor 1, alpha Subunit - genetics, Hypoxia-Inducible Factor 1, alpha Subunit - metabolism, Hypoxia-Inducible Factor-Proline Dioxygenases - genetics, Hypoxia-Inducible Factor-Proline Dioxygenases - metabolism, Male, Mice, Mice, Knockout, MicroRNAs - biosynthesis, MicroRNAs - metabolism, Mixed Function Oxygenases - genetics, Mixed Function Oxygenases - metabolism, Neoplasm Proteins - genetics, Neoplasm Proteins - metabolism, Neoplasm Transplantation, Neovascularization, Pathologic - genetics, Neovascularization, Pathologic - metabolism, Neovascularization, Pathologic - pathology, Prostatic Neoplasms - genetics, Prostatic Neoplasms - metabolism, Prostatic Neoplasms - pathology, Repressor Proteins - genetics, Repressor Proteins - metabolism, RNA, Neoplasm - biosynthesis, RNA, Neoplasm - genetics, Signal Transduction