Preliminary Study On The Associated Non-coding RNA And Its Mechanism In Pancreatic Cancer

BackgroundPancreatic cancer is a common human digestive system malignancy with a high incidence and a fourth mortality rate among all types of malignancies.The current treatment is mainly based on surgery,and many patients in the diagnosis of pancreatic cancer is already late,so the need for more effective early diagnosis and treatment methods are the focus of attention.Autophagy of this biological process,the process is complex and a variety of molecules involved in which in recent years has been gradually revealed that it has the role of regulation of tumor development and prognosis,but in the role of pancreatic cancer and its mechanism is not very clear.At present,with the development of molecular biology,molecular targeted therapy in the treatment of malignant tumors play an increasingly important role,especially in pancreatic cancer.At the same time,more and more information suggests that we will focus ourattention on these key molecules,such as encoded mRNAs and a series of non-coding RNAs that regulate miRNA,lncRNA and circRNA,The complex interaction between the urgent need to be excavated research.In order to clarify the relationship between autophagy and pancreatic cancer and the potential molecular mechanism of autophagy in pancreatic cancer,this study used the combination of cell and molecular biology to select human pancreatic cancer PANC-1 cells as the research object.The related mRNA,miRNA,lncRNA and circRNA involved in the autophagy of pancreatic cancer were explored.Methods1.Pancretic cancer cells PANC-1 were treated with different concentrations of chlorophosphate diphosphate(CDP)and rapamycin,and the autophagy was detected by Western blotting.LC3-? and p62 protein were selected to select the most significant drug concentration on the inhibitory effect and induction of autophagy in the two strains for the follow-up experiments.2.The optimal concentration of pancreas was selected and the PANC-1 cells were treated for 12 hours.And the total RNA was extracted from the chloroquine diphosphate group,the rapamycin group and the untreated blank control group.Using the gene chip technique,the different expression of lncRNAs,miRNAs,circRNAs and mRNAs were detected in three groups.3.Gene Ontology(GO)analysis and Pathway analysis were employed to explore the potential mechanisms.Results1.Chloroquine diphosphate(CDP)could inhibit the autophagy level of PANC-1cells and had the most significant inhibitory effect at 100?M concentration.Rapamycin could induce the autophagy level of PANC-1 cells and the most significant induction at 100 nM concentration.2,After autophagy suppressed,2445 mRNAs were down-regulated,1521 mRNAs were up-regulated,1637 lncRNAs were down-regulated,1547 lncRNAs were up-regulated,4223 circRNAs were down-regulated and5197 circRNAs were up-regulated.Two miRNAs were down-regulated:hsa-miR-663 a and hsa-miR-154-3p.There are 17 potential ceRNAs of hsa-miR-663 a,and their potential regulatory mechanisms in autophagy of pancreatic cancer include cytokine-cytokine receptor interactions and p53 signaling pathways;there are 7 potential ceRNAs of hsa-miR-154-3p,and the potential regulatory mechanism in the process of pancreatic cancer autophagy is the transcriptional pathway of cancer.After autophagy induced,192 mRNAs were down-regulated,302 mRNAs were up-regulated,549 lncRNAs were up-regulated,487 lncRNAs were down-regulated,529 circRNAs were up-regulated,456 circRNAs were down-regulated,and hsa-miR-5787 was up-regulated.There are 9 potential ceRNAs of hsa-miR-5787,and the potential regulatory genes in the process of pancreatic cancer autophagy were TUBA8,UCN2 and CD1 E.ConclusionsMultiple mRNA,lncRNA,circRNA and miRNA are involved in the autophagy process of pancreatic cancer PANC-1 cells and act on a variety of signaling pathways in the form of ceRNA-miRNA-mRNA.They are the potential targets and mechanisms for the diagnosis and treatment of pancreatic cancer.