• Xinquan Wu, Weibo Chen, Huihua Cai, Jun Hu, Baoqiang Wu, Yong Jiang, Xuemin Chen, Donglin Sun, and Yong An.
• Department of Hepatopancreatobiliary Surgery, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
• Arch Med Sci. 2018 Oct 1; 14 (6): 1321-1332.

IntroductionPancreatic cancer is a highly lethal malignancy with high invasion metastasis, which is difficult to diagnose and treat. MicroRNA-216b (miR-216b) plays an important role in many types of tumors. In this study, we explore how miR-216b affected human pancreatic cancer cell development by targeting KRAS.Material And MethodsExpression level of miR-216b and KRAS in tissue samples and cells were detected by RT-PCR and western blot. Immunohistochemical assay analysed the expressions of KRAS protein in tumor and adjacent tissues. The target relationship between miR-216b and KRAS was validated by dual-luciferase reporter assay. Pancreatic cancer cell proliferation, migration, invasion and apoptosis abilities of cells transfected with miR-216b mimics and KRAS-siRNA, Panc-1 were detected by MTT assay, transwell assay and flow cytometry assay respectively. Prognosis of patients with different expression levels of miR-216b and KRAS were analyzed by Kaplan-Meier survival analysis and Cox proportional hazards regression model.ResultsThe expression of miR-216b in pancreatic cancer tissue and cell line was down-regulated (p < 0.01), while KRAS expression was up-regulated (p < 0.01) compared with adjacent normal tissues. Both the expressions of miR-216b and KRAS have a strong influence on prognosis of the pancreatic cancer patients (p = 0.024 and p = 0.017). The dual-luciferase reporter assay verified that miR-216b directly targeted KRAS in pancreatic cancer cells. Overexpression of miR-216b reduced the expression of mRNA and protein of KRAS (p = 0.013 and p = 0.003), but silencing KRAS had no effect on miR-216b expression (p = 0.706). By silencing KRAS or up-regulation of miR-216b could suppress cell proliferation, migration and invasion of pancreatic cancer cells and promote apoptosis.ConclusionsMiR-216b might inhibit pancreatic cancer cell progression and stimulate apoptosis by silencing KRAS.

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