Application Of MicroRNAs In The Occurrence And Early Diagnosis Of Pancreatic Cancer

Background Pancreatic cancer is one of the most malignant tumors with poor prognosis.It is also the fourth leading cause of cancer-related death and the second malignancy in gastrointestinal neoplasm. As most of the pancreatic cancer patients are diagnosed at the advanced stage,they often lose the chance to be resected radically.Thus, the5-year survival rate of pancreatic cancer is extremely low,even no more than5%.However,the therapeutic effect of early pancreatic cancer is surprisingly good that the5-year survival rate could be100%at most.The early diagnosis of pancreatic caner is very helpful in improving the survival rate and ameliorate the prognosis.But as there are still lack of sensitive and specific tools of early detection in pancreatic cancer,the early diagnosis becomes very difficult. Conventional examinations such as enhanced CT/MRI and serum CA199have limitations in early diagnosis.Therefore,looking for new approaches of early diagnosis of pancreatic caner has become a hot topic in present research.MicroRNAs (miRNAs) are a group of small RNAs, which widely exist in eukaryon and consist of18-22nucleotides (-22nt).They are noncoding RNA with regulatory function,which are closely related to tumor occurrence and are candidates of tumor biomarkers.MiRNAs regulate gene expressions by completely or incompletely pairing to3’UTR(3’-untranslated region) of target mRNA,causing inhibition of their translation to functional proteins or degradation of mRNA.MiRNAs play an important role in regulating cell differentiation,proliferation and apoptosis.The present studies have proved the intimacy of miRNAs and occurrence of pancreatic tumors,and found that the expressions of miRNAs in different stage of tumors are significantly different.What is more,miRNAs are widely and stably presented in plasma,pancreatic juice and feces.The tissue specificity and high stability of miRNAs make them to be the potential biomarkers.Objective1、To explore the dynamic change of miRNAs in occurrence of pancreatic cancer.2、To find the serum specific miRNAs which would be the potential biomarkers of pancreatic cancer.3、To identify and validate the value of miRNAs in early diagnosis of pancreatic cancer.Methods 1Establish SD rat animal model of pancreatic cancer induced by chemical carcinogen DMBA.2Taqman miRNA array was used to test the rat model of pancreatic cancer;miRNA profile was screened in all time points.3STC was used to analyze the tendency and significance of miRNA expression in the time sequence.4The biological information method(TargetScan) was used to find out the target genes of miRNA.Cancer-related target genes were screened out.5Five miRNAs which were regarded as tumor-related miRNAs in the literature were validated.Results1By using5mg dose of DMBA with a low non-experimental accidental death rate and a high tumorigenic rate,we induced the rat models of pancreatic cancer successfully. After2weeks, the incidence of cancer was37.5%(6/16) in DMBA experimental group, accompanied by3cases of moderate-level of Pan IN;After1month,the incidence of cancer was76.5%(13/17) in experimental group.2miRNA array was used to test the expression levels of miRNAs in all time points(0w,2w&1m) of pancreatic tissue.20miRNAs were screened out respectively in the2-week and1-month pancreatic tissue in DMBA experimental group.27miRNAs and14miRNAs were screened out respectively in the2-week and1-month blood in DMBA experimental group.316tendencies were obtained by STC analyzing,and according to P-value,we got35miRNAs in pancreas and12miRNAs in blood.4Target genes of miRNAs were predicted by TargetScan,and the tumor-related genes were screened out.5Five cancer-related miRNAs were testified by real-time quantitative PCR.Conclusion1. We have successfully established the rat model of of pancreatic cancer,which makes it possible to study the occurrence and progression of pancreatic cancer dynamically.2. We have preliminarily get miRNA expression profile of ealy panceatic cancer,3. miRNA is able to be the serum biomarkers of early stage of pancreatic cancer,which is of great clinical value.