Fig. 8.

The schematic model for STAT3‐miR‐223‐TGFBR3/HMGCS1 axis in CSCC development. In CSCC cells, IL‐6‐induced STAT3 activation is enforced by HPVs E6 protein. Upregulated phosphorylation of STAT3 enters into nuclear to bind on the promoter of miR‐223 and accelerates its expression. Increased miR‐223 inhibits TGFBR3 and HMGCS1 expression through promoting TGFBR3 or HMGCS1 mRNA degradation in cytoplasm. Downregulated TGFBR3 or HMGCS1 lose its effect on inhibiting β‐catenin accumulation or promoting phosphorylation of p27 and CHK2. In microenvironment, exosomal miR‐223 induces IL‐6 expression in monocyte/macrophage promoting STAT3 activation in CSCC cells.