Expression And Role Of MiR-24-3p In Pancreatic Cancer

Background: pancreatic ductal adenocarcinoma(PDAC)is a kind of malignant tumor which is very difficult to diagnose and treat.Because lack of early detection,intrinsic resistance to most chemo-/radio-and immunotherapy strategies,the 5-year survival rate is less than 5%.At present,the morbidity rate of pancreatic cancer has a significant increase in the trend,and the etiology is not clear.micro RNAs(mi RNA)is considered to be a new biomarker,it is a small molecule single-stranded RNA(ss RNA)consisting of18-22 nucleotides,which regulates the transcription expression of multiple genes.Increasing evidence indicates that mi RNAs play critical roles in malignant transformation,tumor progression and metastasis.Aberrant mi R-24-3p expression has been associated with several cancers.However,it is still unclear whether mi R-24-3p regulates pancreatic cell proliferation and apoptosis or not.Therefore,it is urgent to identify useful molecular targets for diagnosis and treatment of pancreatic cancer as early as possible.Aim: To investigate the expression of mi R-24-3p and its clinical significance in pancreatic cancer and the role of mi R-24-3p in regulation of pancreatic cell proliferation and apoptosis.Methods: The expression of mi R-24-3p in 57 pairs of fresh frozen pancreatic ductal adenocarcinoma(PDAC)specimens and their corresponding adjacent non-cancerous pancreas specimens was detected by quantitative real—time PCR(q RT-PCR).Then,the patients were divided into high and low expression groups.The correlation between the expression of mi R-24-3p and the clinicopathological characteristics was analyzed by Chi-square test.Survival curves were plotted using the Kaplan-Meier method,then univariate analysis of all variables was made using the Logrank test.The expression of APAF1 was detected by q RT-PCR and the protein expressions was determined by Western blot.Cell proliferation was detected with CCK8,cell migration abilities were evaluated by transwell assay,apoptosis and cell cycle was investigated using flow cytometry.Results: The expression of mi R-24-3p in PDAC tissue was up-regulated compared to their corresponding adjacent non-cancerous tissue(p<0.05).The expression of mi R-24-3p was not correlated with age,gender,tumor differentiation,tumor location and vascular invasion(p>0.05).However,mi R-24-3p expression was positively associated with tumor size,TNM stage,lymph node metastasis.And the prognosis of mi R-24-3p high expression group was poor than mi R-24-3p low expression group.Overexpression of mi R-24-3p can inhibit APAF1 gene expression in pancreatic cancer cells.What's more,overexpressed mi R-24-3p can accelerated the proliferation and migration of pancreatic cancer cells.Moreover,mi R-24-3p can repress apoptosis of pancretic cancer cells,which is similar to si APAF1.Conclusion: mi R-24-3p was significantly up-regulated in PDAC tissue,it might contribute to the development and progression of PDAC and might play a role of an oncogenic regulator by directly targeting APAF1 in pancretic cancer.It may be a novel biomarker in diagnosis and treatment of pancreatic cancer.