Promotes the Malignancy Progression of Pancreatic Ductal Carcinoma by Inhibiting the Expression of p27 and PPP2R2A via G1/S Cell Cycle Pathway.

OBJECTIVE

To investigate the effect of on the malignant biological behavior of pancreatic cancer, and to explore the target genes and pathways directly affected by , to provide new therapeutic ideas and targets for the study of the diagnosis and treatment of pancreatic cancer.

METHODS

We used qRT-PCR to measure expression quantities. We used cell cycle, CCK-8, clonal formation to verify the change of proliferation capacity of PC cells. We used transwell assay to detect the migration and invasion of PC cells. We used the bioinformatics tool TargetScan (http://www.targetscan.org) to identify the possible target genes of . Immunohistochemistry revealed the clinicopathological significance of PPP2R2A, p27 and in the expression of pancreatic cancer. Western blot was used to detect the expression changes of PPP2R2A, p27 and G1/S cell cycle pathway-related proteins CDK2, cyclinE2 and p21 after transfection of mimics and inhibitors of

RESULTS

According to our study, expression was significantly higher in PC tissues than that in paired normal pancreas, which was associated with PC tumor size (=0.042) and preoperative CA19-9 level (=0.046) of PC patients. Its overexpression promoted PC cell proliferation, invasion and migration following with the p27 and PPP2R2A protein downregulation in Capan-2, PANC-1 and BxPC-3 cells, and vice versa. Bioinformatics analysis and dual-luciferase reporter assay further confirmed that and were direct target genes of . The negative relationship of with p27 and PPP2R2A was also observed in PC tissues.

CONCLUSION

promotes the proliferation, migration and invasion of pancreatic cancer cells. directly downregulated and and via the G1/S cell cycle pathway to promote the development of pancreatic cancer.