Meanwhile, UCA1 expression negative-correlated with p27 in PC tissues (r<sup>2</sup>=0.46, p<0.01), and knockdown of p27 partly abrogated the cell proliferative activities caused by UCA1 (p<0.05).
This increased risk was more pronounced in carriers with the p27 homozygous wild type (ORadjusted, 2.20; 95% CI, 1.32-3.68) and in nonsmokers (ORadjusted, 2.16; 95% CI, 1.14-4.10), although the p27 polymorphism alone was not associated with pancreatic cancer risk.
These in vitro characteristics translated to increased tumor growth in both subcutaneous and orthotopic pancreatic cancer murine models and also led to increased liver metastasis. mTrop2 expression also increased the levels of phosphorylated ERK1/2 mediating cell cycle progression by increasing the levels of cyclin D1 and cyclin E as well as downregulating p27.
Our findings suggest that the p21 polymorphism independently and p21 and p27 polymorphisms jointly contribute to a significantly earlier age at diagnosis of pancreatic cancer.