Expression Of Hsa-mir-196b In Pancreatic Cancer And Its Effect On Biological Behavior Of Pancreatic Cancer

Aim:To establish the differential expression profile of miRNA in pancreatic cancer,and to explore the mechanism of miR-196 b in the progression of pancreatic cancer.Method:1.Three pairs of pancreatic cancer tissues and adjacent tissues were selected randomly,and the miRNA expression profiles of the pancreatic cancer tissues and the adjacent tissues samples were sequenced by the next generation sequencing(Illumina Hise-2500),and the differential expression profiles of mi RNA were screened.2.The significant differentially expressed miRNA was analyzed by the relevant software and websites,finding out the most valuable target miRNA.The relationship between target miRNA(hsa-mir-196b)and pathologic grading and clinical stage of pancreatic ductal epithelial cell carcinoma was further analyzed,and the RT-PCR in 15 pairs samples were used to verify the differential expression of hsa-mir-196 b in PDAC and adjacent tissues.3.To explore the regulation mechanism of hsa-mir-196 b and the biological behavior of pancreatic cancer cell.Double luciferase reporter gene and Western Blot were used to verify that HOX B6 is the downstream target gene.We further discussed the correlation between the expression of HOX B6 and the clinicopathological characteristics and prognosis of pancreatic cancer.Result:1.There were differences in the expression of miRNA between pancreatic cancer tissues and adjacent tissues.There were 579 independent known miRNA in the three pairs of pancreatic cancer tissues and adjacent tissues by the next generation sequencing,133 of them were found in a significant difference.In the end,the known miRNA expression of stable expression and up expression of miRNA in each group(2): hsa-mir-31;hsa-mir-196b;the down expression of miRNA(6): hsa-mir-148a;hsa-mir-141;hsa-mir-217;hsa-mir-216b;hsa-mir-802;hsa-mir-216 a.2.The correlation between hsa-mir-196 b and tumor survival was best,and it was related to histological grade,pathological stage,M stage and T staging of tumor(p<0.05),and RT-PCR was used to verify the expression of has-miR-196 b in 15 pairs of pancreatic cancer tissues and adjacent tissues.Compared with the adjacent tissues,the expression of has-miR-196 b in pancreatic cancer group was significantly increased,which was consistent with the sequencing results,and the difference was statistically significant(P < 0.05).3.Hsa-miR-196 b has the ability to promote the proliferation,invasion and migration of pancreatic cancer cells,and the HOX B6 gene is the downstream target gene of hsa-miR-196.hsa-miR-196 can bind to the 3 '-UTR region of HOX B6 and play a direct inhibitory effect on the HOX B6 gene;The expression of HOX B6 is lower in pancreatic cancer cells than the normal ductal epithelial cell carcinoma.There was a significant correlation between expression of HOX B6 and the survival time of pancreatic cancer patients,the prognosis of patients with higher expression of HOX B6 was better.Conclusion:1.In this study,the specific differential miRNA expression profiles of human pancreatic cancer tissues and adjacent tissues were established by the next generation sequencing,which provided a basis for further study of the role of miRNA in pancreatic cancer.The analysis showed that the expression of has-miR-196 b in pancreatic cancer tissues was higher than that of para cancerous tissue,and it might play a role as an oncogene in the carcinoma.2.It is the first time to show that HOX B6 plays as a tumor suppressor in pancreatic cancer.3.It is the first time to show that has-miR-196 b can regulate the expression of the downstream HOX B6 by targeting and may activate the ERK signaling pathway and P38 signaling pathway to promote the proliferation,migration and invasion of pancreatic cancer cells to play as an oncogene in pancreatic cancer.