Micro RNA-141 Suppresses Proliferation,migration In Pancreatic Cancer By Targeting Oncogene Bmi-1

[Background] Pancreatic cancer(PC)is one of the worst malignant tumors.Traditional methods of treatment have not played an expected role in the diagnosis and treatment of pancreatic cancer.There is an urgent need to develop new therapeutic directions and therapeutic targets.Micro RNA(mi RNA)has attracted more and more attention due to its close relationship with the occurrence and development of tumors.At least 50% of abnormally expressed mi RNAs in tumors can act as post-transcriptional regulators and play an important role.Micro RNA exhibits oncogenic or tumor suppressive activity by directly binding the m RNA of a target gene.The Bmi-1 is a member of the polycomb group genes(Pc G).Bmi-1 was found to be involved in the development and progression of various tumors.[Objective]The purpose of this research was to investigate the mechanism of mi R-141 functioned as a tumor suppressor by targeting the oncogene Bmi-1.[Methods] 1.Analysis of pancreatic cancer mi RNA expression microarrays downloaded from the GEO database.The expression of mi R-141 in PC cells and normal pancreas cells were detected by quantitative real-time PCR(q RT-PCR).2.Analysis of expression of Bmi-1 in tumor tissues and normal samples using m RNA expression profiles of pancreatic cancer downloaded from GEO Database.Analysis of the correlation between the mi R-141 and Bmi-1 by microarray.3.The influence of upregulating mi R-141 on cell proliferation was tested by Counting Kit-8.Colony-formation assays was made to investigate the clone formation capacity.Transwell experiments were used to observe the effect of up-regulation of mi R-141 on the migration of pancreatic cancer cells.4.The influence of down-regulating Bmi-1 on cell proliferation was performed by Counting Kit-8.Colony formation assays was made to investigate the clone formation capacity.Transwell experiments were also used to observe the effect of knockdown of Bmi-1 on the migration of pancreatic cancer cells.5.Bioinformatics database searched for possible binding sites between mi R-141 and Bmi-1.Dual-luciferase report gene assay was used to demonstrate the binding site between mi R-141 and Bmi-1.The protein expression of Bmi-1 was detected by western blot after up-regulating mi R-141.6.Up-regulating Bmi-1 and co-transfect with mi R-141 mimic to observe the change of proliferation and migration in pancreatic cancer cells.[Results]1.Based on analysis of two sets of pancreatic cancer-associated mi RNA expression microarrays,mi R-141 was down-regulated in pancreatic cancer.2.Bmi-1 was up-regulated in pancreatic cancer tissues and cells.Analysis of correlation showed that the expression of Bmi-1 was inversely related to mi R-141 in pancreatic cancer.3.Up-regulation of mi R-141 reduced proliferation,colony formation and migration in pancreatic cancer cells.4.Down-regulation of Bmi-1 inhibited proliferation and migration in pancreatic cancer cells,similar to the result of overexpression of mi R-141.5.Dual-luciferase report gene assay suggested that there was a binding site between mi R-141 and Bmi-1.After overexpression of mi R-141,the protein expression of Bmi-1 was decreased.6.Overexpression of Bmi-1 can reverse the inhibitory effect of mi R-141 on proliferation and migration in pancreatic cancer.[Conclusion] Mi R-141 shows low expression in pancreatic cancer and plays a tumor suppressive role in pancreatic cancer.The expression of Bmi-1 in pancreatic cancer showed an abnormally increasing trend,and there was a negative correlation between mi R-141 and Bmi-1.We found that mi R-141 can inhibit the growth of pancreatic cancer cells by targeting Bmi-1.This suggested that mi R-141/Bmi-1 may become a new target for gene therapy in pancreatic cancer and open a new path for the diagnosis and treatment of pancreatic cancer.