Figure 7
From: Hypoxia-inducible miR-182 enhances HIF1α signaling via targeting PHD2 and FIH1 in prostate cancer
miR-183-96-182 and HIF1α expression were upregulated in PTENPC−/− mice.
(a) Immunohistochemical staining of HIF1α. Theprostate tissues were stained by HIF1α antibody. (b) RT-PCR analysis of miR-183-96-182 in prostate tissues from PTENPC−/− mice (n = 3). The expression level of miR-210 was also determined. (c,d) The expression of PHD2, FIH1 (c) VEGF and CD31 (d) in prostate tissues was determined by RT-PCR. Data are mean ± SEM (n = 3). *p < 0.05, **p < 0.01. (e) The model of HIF1α-miR-182 positive feedback loop pathway. Decrease in oxygen level or loss of PTEN, which leads to PI3K/Akt activation, in prostate cancer increases HIF1α protein level, which upregulates miR-182 expression at transcriptional level. Increased miR-182 expression represses PHD2 and FIH1 expression by directly targeting their 3′-UTR, which results in an accumulation of HIF1α protein. This positive feedback loop maintains hyperactive HIF1α signaling in prostate tumors, which facilitates angiogenesis and tumor growth in hypoxic environment.
