Proteasomal degradation is often regulated by phosphorylation [158], and blocked activation of the Akt and ERK1/2 pathways caused by miR-145-mediated N-RAS and insulin receptor substrate 1 (IRS1) expression inhibition was confirmed to suppress the expression of HIF-1α and downstream VEGF in restricted colorectal cancer growth, which is speculated to depend on its interference with the normal HIF-1α protein degradation process [148]; in addition, almost the same signaling initiated by miR-30e can be seen in breast cancer [149]. The gene discussed is IRS1; the disease is breast carcinoma.