Figure 2.

The miR-506 network regulates EMT and cellular senescence. miR-506 directly targets SNAI2[28], vimentin[29], N-cad[29], NFκB[37] and CDK4/ CDK6[34]. miR-506 down-regulates SNAI2 which increases E-cad expression and subsequently promotes cell-cell adherence[28]. miR-506 directly down-regulates vimentin and N-cadherin, which reduces cell mobility and cell-matrix adherence[29]. miR-506 also targets NFκB p65[37] which transactivates N-cad and vimentin and is implicated in the regulation of EMT[38,39]. miR-506 inhibits the expression of FoxM1 by directly down-regulating CDK4/CDK6, which not only promotes cellular senescence[34] but also inhibits EMT via suppressing the expression of SNAI1 and ZEB1/2[36]. Therefore, miR-506 inhibits cancer progression through suppressing EMT and promoting cellular senescence. Decreased expression of miR-506 partially results from promoter methylation[28]. EMT, epithelial-to-mesenchymal transition; E-cad, E-cadherin; SNAI2, snail family zinc finger 2; N-cad, N-cadherin; NFκB, nuclear factor kappa B; CDK4, cyclin-dependent kinase 4; CDK6, cyclin-dependent kinase 6; FoxM1, Forkhead box protein M1; SNAI1, snail family zinc finger 1; ZEB1, zinc finger E-box binding homeobox 1; ZEB2, zinc finger E-box binding homeobox 2; ILK, integrin-linked kinase; GSK-3β, Glycogen synthase kinase 3β.