Western blot analysis showed that enforced expression of miR-192 decreased the expression of smad-interacting protein 1 (SIP1) and altered a set of cell cycle-related genes in the PANC-1 cells. miR-192 overexpression increased tumor volume in an orthotopic pancreatic cancer mouse model, coupled with suppression of SIP1 and elevation of collagen I.
However, most pancreatic cancers express miR-200a and miR-200b, but this expression does not affect SIP1 expression, as the SIP1 promoter is silenced by hypermethylation and in these cancers E-cadherin is generally expressed.
Taken together, these results suggest that SIP1 is involved in the progression of pancreatic cancer and plays a role in mediating signal transduction from collagen type I to downregulate E-cadherin expression.