| Background and purpose: Pancreatic cancer is a malignant tumor of the digestive tract system,its treatment effect is not good,and it lacks effective diagnostic and prognostic markers.In this paper,we evaluated the value of long non-coding RNA(lncRNA)and micro RNA(miRNA)and as prognostic markers in pancreatic cancer.In addition,we focused on the function and mechanism of LINC01060 in pancreatic cancer.Methods: In the first two chapters,we used the pancreatic cancer expression profile data from the TCGA database to identify differentially expressed mRNAs,lncRNAs,and miRNAs in pancreatic cancers,and screened for the key noncoding RNAs in pancreatic cancers using ce RNA and gene co-expression theory.Next,we determined the lncRNA and miRNA that can be used as markers for prognostic evaluation of pancreatic cancer through a COX hazard ratio regression model.In addition,we also conducted a preliminary analysis and discussion of the function of noncoding RNAs in pancreatic cancer in the model.In Chapter 3,we investigated the function and mechanism of LINC01060 in pancreatic cancer through in vitro and in vivo experiments.Results: Frist,we established a pancreatic cancer risk prognostic evaluation model based on the expression levels of LINC00460,C9orf139,and MIG600 HG from lncRNAs that are differentially expressed between pancreatic cancer and adjacent tissues,and evaluated the effectiveness of the model.Second,we established a pancreatic cancer risk prognosis evaluation model based on the expression levels of mi R-203,mi R-424,mi R-1266,mi R-1293,and mi R-4772 from miRNAs that are differentially expressed between pancreatic cancer and adjacent tissues,and evaluated the effectiveness of the model.Third,we found that LINC01060 acts as a tumor suppressor gene in pancreatic cancer,which suppresses the malignant progression of pancreatic cancer by regulating focal adhesion turnover.Conclusion: We found that LINC0046,C9orf139,and MIG600 HG are potential predictive markers among lncRNA for the risk assessment of postoperative patients with pancreatic cancer.We found that mi R-203,mi R-424,mi R-1266,mi R-1293,and mi R-4772 are potential predictive markers among miRNAs for the risk assessment of postoperative patients with pancreatic cancer.LINC01060 plays an important role in inhibiting the progression of pancreatic cancer by regulating Vinculin expression,and LINC01060-Vinculin-Focal adhesion axis is a potential target for the treatment of pancreatic cancer.Chapter 1 Screening of Prognostic Related lncRNA in Pancreatic CancerBackground and purpose: In this chapter,we analyzed the value of lncRNA for prognostic evaluation of pancreatic cancer by analyzing gene expression profile data.Methods: First,we screened differentially expressed mRNA,miRNA,and lncRNA between pancreatic cancer tissues and adjacent tissues using transcriptome data from the TCGA database.Subsequently,we constructed a lncRNA-miRNA-mRNA co-expression network based on the competitive endogenous RNA theory using mi Rcode,mi RDB,mi RTar Base,and Target Scan databases.Finally,by incorporating lncRNA related to the overall survival of pancreatic cancer patients in the network into the COX proportional hazard regression model,we established a lncRNA-based pancreatic cancer prognostic evaluation model.In addition,in this chapter,we also discussed the possible functions of lncRNA in pancreatic cancer and the signaling pathways involved in prognostic assessment models.Results: The lncRNA-miRNA-mRNA network consisting of 43 lncRNA nodes,11 miRNA nodes,253 mRNA nodes,and 475 edges was constructed.Survival analysis results showed that among 46 lncRNAs in the ce RNA network,HOTTIP,ABHD11-AS1,MIR205 HG,LINC00460,MIR600 HG,and C9orf139 were related to overall survival.COX proportional hazard regression analysis showed that LINC00460,MIR600 HG,and C9orf139 could be used to construct a prognostic risk assessment for pancreatic cancer.Kaplan-Meier survival curve analysis showed that the median survival time and five-year survival rate of the high-risk group in this model were significantly higher than the low-risk group.Conclusion: The results of this chapter show that the pancreatic cancer prognostic assessment model composed of LINC0046,C9orf139,and MIG600 HG can effectively stratify patients for pancreatic cancer after surgery.LINC0046,C9orf139,and MIG600 HG are potential joint predictive markers for risk assessment of patients with pancreatic cancer after surgery.Chapter 2 Screening of Prognostic Related Micro RNA in Pancreatic CancerBackground and purpose: In this chapter,we analyze the value of miRNAs for the prognostic evaluation of pancreatic cancer by analyzing data from gene expression profiles.Methods: We used differentially expressed miRNAs from the pancreatic cancers screened in Chapter 1.We screened these differentially expressed miRNAs by univariate and multifactorial COX regression analysis and established a proportional hazard prediction model.Then,through miRNA target gene prediction,GO analysis,KEGG pathway analysis,protein-protein interaction analysis,and gene co-expression analysis,the signal pathways and functions of miRNAs in the pancreas were studied.In addition,we verified the expression of 5 miRNAs in 20 pancreatic cancer tissues in the model using quantitative PCR.Results: Through COX regression analysis,we found that mi R-203,mi R-424,mi R-1266,mi R-1293,and mi R-4772 can be used to construct a proportional hazard prediction model that effectively predicts the overall survival of pancreatic cancer patients.After using this model to calculate the risk value of patients with pancreatic cancer,patients with pancreatic cancer were divided into high-risk group(n = 88)and low-risk group(n = 89)according to the level of risk,and the 5-year overall survival rate of the two groups 10.2% and 47.8%,respectively.Functional enrichment analysis showed that the five miRNAs involved in the model construction were involved in signal transduction pathways such as PI3K-AKT,TGF-?,and pluripotent stem cells.Conclusion: The results of this chapter show that pancreatic cancer prognostic assessment models composed of mi R-203,mi R-424,mi R-1266,mi R-1293,and mi R-4772 can effectively stratify patients for pancreatic cancer after surgery.mi R-203,mi R-424,mi R-1266,mi R-1293,and mi R-4772 are potential combined predictive markers of risk assessment for patients with pancreatic cancer after surgery.Chapter 3 Study on the Function and Mechanism of LINC01060 in Pancreatic CancerBackground and purpose: The function of long non-coding RNA has received more and more attention,but its role in pancreatic cancer remains to be further studied.This chapter first investigates the function and mechanism of long intergenic non-protein coding RNA 1060(LINC01060)in pancreatic cancer.Methods: First,we analyzed the differentially expressed lncRNA in pancreatic cancer using GEO data,and found that the expression of LINC01060 in pancreatic cancer tissues was significantly lower than that in adjacent tissues.Subsequently,we tested the expression of LINC01060 in 90 pancreatic cancer tissue chips by in situ hybridization experiments,and analyzed the relationship between the expression of LINC01060 and the clinicopathological characteristics of pancreatic cancer.In addition,we have further studied the function and mechanism of LINC01060 in pancreatic cancer through in vitro and in vivo experiments.Results: This study found that the expression of LINC01060 in pancreatic cancer tissues was lower than that in adjacent tissues,and its low expression in patients with different pancreatic cancer was significantly associated with poor prognosis.Through further experiments,we found that LINC01060 regulates the expression of Vinculin through RNA levels,thereby inhibiting the proliferation,invasion and metastasis of pancreatic cancer;overexpression of Vinculin can inhibit the increase of FAK and Paxillin phosphorylation mediated by LINC01060 down-regulation,thereby reversing LINC01060-mediated inhibition of FAK turnover.In addition,down-regulation of Vinculin can promote the proliferation of pancreatic cancer cells by up-regulating ERK activity and inhibit the function mediated by up-regulation of LINC01060.Conclusion: This study found that LINC01060 has an important role in inhibiting the progression of pancreatic cancer by regulating Vinculin expression.LINC01060-Vinculin-Focal adhesion axis is a potential target for the treatment of pancreatic cancer.Chapter 4 Advances in Pancreatic Cancer and Non-coding RNA ResearchDeepening the understanding of pancreatic cancer development and other aspects will help us to make progress in improving the prognosis of pancreatic cancer.This chapter reviews important advances in the field of pancreatic cancer research,including research advances in pathogenesis,tumor microenvironment,biomarkers for diagnosis and prognosis,surgical treatment,adjuvant and neoadjuvant therapy,and targeted therapy.The discovery of non-coding RNA has greatly improved the understanding of disease for researchers,and it has become one of the hottest topics in the field of life science research.This chapter also summarizes the research progress of miRNA,lncRNA and other non-coding RNAs. |
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