[Correlation between miR-1178 expression and clinicopathological significance in human pancreatic cancer]

Objective: To test the expression of miR-1178 in pancreatic cancer and study its clinicopathological significance and mechanism. Methods: The expression of miR-1178 in 87 paired paraffin pancreatic ductal adenocarcinoma specimens and adjacent non- cancerous pancreatic tissue diagnosed by Pathology Department of Peking Union Medical College Hospital was detected by hybridization in situ. The relationship between the expression of miR-1178 and clinicopathological characters was analyzed.miR-1178 mimics and inhibitor were used to further detect the close relationship among miR-1178 and cancer invasion. Establish a nude mice subcutaneously transplanted tumor model, 4 weeks after vaccination for tumor volume and weight measurement.Student t-test, rank sum test, and χ(2) test was used respectively to compare the data between two groups. Cox regression was adopted to improve the single factor and multiple factors analysis. Results: The results of hybridization in situ showed the expression of miR-1178 was increased in 72 cases with pancreatic cancer compared to that in paired normal pancreatic tissues (50/72 vs. 11/72, χ(2)=43.26, P<0.05). miR-1178 expression was positively associated with tumor lymph node stage (χ(2)=4.189, P=0.041). Univariate and multivariate analysis revealed that miR-1178 was an independent adverse prognostic indicator for patients with pancreatic cancer (HR=2.364, 95%CI: 1.114-5.019, P=0.025). Transwell assay indicated the over-expression of miR-1178 increased the number of AsPC-1 cells that penetrated the ECM-coated membrane (177.0±19.8 vs. 119.7±15.9)(χ(2)=8.21, P<0.05). For the in vivo experiment, overexpression of miR-1178 significantly promoted tumor growth, compared with control group (tumor volume: (5 122.4±760.2)mm(3) vs. (1 976.8±601.8)mm(3), t=2.413, P<0.05; tumor weight: (1.55±0.21)g vs. (0.67±0.17)g, t=2.960, P<0.05). Over-expression of miR-1178 down-regulated the expression of Stub1 and elevated the expression of FAK/MMP-9 signal pathway(P<0.05). Conclusions: MiR-1178 is overexpressed in pancreatic cancer, and is effective for predicting patients' prognosis. MiR-1178 regulate Stub1/FAK/MMP-9 signal pathway and promote the invasion of AsPC-1 cells.