Figure 4: Drosha and Dicer downregulation under hypoxia leads to increased epithelial-to-mesenchymal transition.
From: Hypoxia-mediated downregulation of miRNA biogenesis promotes tumour progression
Expression of significantly altered pro-miRNAs (a) and metastatic genes (b) in Dicer and Drosha knocked down A2780 cells under normoxia (data shown normalized to siControl) or ectopic expression of Dicer and Drosha under hypoxia (data shown normalized to control), N, normoxia; H, hypoxia. E-cadherin and vimentin mRNA (c) and protein (d) expression levels under hypoxic exposure in A2780 cells. Blue, nucleus. Scale bar, 200 μm. (e) mRNA levels of E-cadherin and vimentin in A2780 mouse tumour samples treated with bevacizumab. (f) E-cadherin (top) and vimentin (bottom) expression after knockdown of Dicer, Drosha, or both, using siRNAs in A2780 cells. (g) Effect of Drosha and Dicer on cell migration and invasion in A2780 cells. Drosha and Dicer levels were downregulated using siRNAs under normoxic conditions. Rescue of Drosha was achieved using siRNAs against ETS1 and ELK1 under hypoxic conditions. (h) Pearson correlation between E-cadherin or vimentin and hypoxia marker CA9 expression in clinical ovarian tumour samples (n=30). All images shown are representative and data are presented as mean±s.e.m. of n≥3 experimental groups. *P<0.05, **P<0.01, ***P<0.001 (Student t-test).
