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Research On Long Non-coding RNA Regulatory Function Prediction In Gastric Cancer

Posted on:2020-09-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:H M LiuFull Text:PDF
GTID:1364330602455533Subject:computer science and Technology
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Gastric cancer is one of the most common cancers and death rates worldwide,with nearly half of them occurring in East Asia,especially in China,South Korea,Japan,and Mongolia.According to the latest data published by the National Central Cancer Registry(NCCR)in 2018,gastric cancer has become the third common cancer and the third incidence of cancer in China.Especially in the northwestern part of China,the incidence of gastric cancer has surpassed that of lung cancer,and the mortality rate is the same as that of lung cancer.At home and abroad,a large amount of human,material and financial resources have been invested in research.Although there have been advances in clinical diagnosis,treatment,and prevention,there are not many high-quality methods for early intervention of gastric cancer at present,and the costbenefit ratio of advanced diagnosis and treatment is very low.Gastric cancer not only causes great pain to patients but also imposes a heavy burden on the medical system.Therefore,comprehensive control of the regulation mechanism of gastric cancer is of great significance for the diagnosis and treatment of gastric cancer.Long non-coding RNA(lncRNA),an important subclass of non-coding RNA,is longer than 200 nucleotides,and lack protein-coding capability.The regulation function of lncRNA is extremely complex.It can interact with various biomolecules,participate in epigenetic modification,transcriptional regulation,RNA editing,and protein translation regulation.LncRNA plays a key regulatory role in tumor growth and metastasis,and can be sensitively involved in the process of tumor development.Therefore,lncRNA can be used as a tumor biomarker in the clinical diagnosis,prognosis,and treatment of tumors.The study of lncRNA brings further hope for the regulation of tumors and the diagnosis and treatment of cancer patients.With the rapid development of biotechnology and information technology,bioinformatics has made great progress as an independent subject.It has become an important subject that cannot be replaced by any single subject.It can provide new opportunities for tumor-related lncRNA function prediction and provide accurate research objects for biological experiments.However,the current lncRNA functional studies tend to focus on a small number of classical lncRNAs,accounting for less than 1% of the known lncRNAs.The majority of lncRNAs function remain unclear,lacking an effective exploration of the combination of bioinformatics and biological experiments.Therefore,the prediction of lncRNA regulatory function based on bioinformatics methods is extremely important for the understanding of the regulation mechanism of gastric cancer.Studies have shown that lncRNA plays an important regulatory role in the development of tumors by competing endogenous RNA(ceRNA)mechanisms.In the related research of gastric cancer,limited by the source of data,data processing methods,experimental conditions,and other factors,the mechanism of lncRNA in the ceRNA regulatory network of gastric cancer is still unclear.In addition,some researchers have identified through bioinformatics methods that some lncRNA might be used as biomarkers for the diagnosis and prognosis of gastric cancer.However,due to experimental technical conditions and other factors,the study of lncRNA in gastric cancer often cannot effectively combine bioinformatics with biological experiments,and the regulatory function of lncRNA in gastric cancer has not been confirmed.Therefore,there are still many problems in the field of lncRNA function prediction in gastric cancer.Based on the above problems,this article effectively integrates bioinformatics methods and biological experimental techniques,starting with the gastric cancer data obtained from The Cancer Genome Atlas(TCGA)database.Then,this article predicts the potential function of lncRNA in the development of gastric cancer through data processing,clinical information analysis,regulatory network construction and analysis,and functional enrichment analysis.Finally,this article validated the regulatory function of lncRNA by designing biological experiments.The article mainly includes the following two aspects.1.Construction and functional prediction of ceRNA regulatory network in gastric cancerBased on the ceRNA mechanism,this article firstly obtained the gastric cancer gene expression data from the TCGA database,and identified lncRNA,microRNA(miRNA)and message RNA(mRNA)which are significantly differentially expressed in gastric cancer,as potential nodes in the gastric cancer ceRNA regulatory network.Then,the ceRNA regulatory network was constructed by introducing significant co-expression characteristics of lncRNAmiRNA-mRNA.The results of functional enrichment analysis showed that the ceRNA regulatory network of gastric cancer was closely related to cancer.Through the evaluation strategy of complex network node importance,we found that RP5-1120P11,DLEU2,and DDX11-AS1,as potential hub lncRNAs,might be involved in the whole ceRNA network.Finally,the biological experiments demonstrated that the high expression of DLEU2 and DDX11-AS1 in gastric cancer tissues.DLEU2 and DDX11-AS1 can promote the proliferation of gastric cancer cells,and can participate in the ceRNA mechanism of gastric cancer by affecting the expression level of miRNA.This article systematically integrates bioinformatics and biological experimental methods,and effectively constructs and experimentally demonstrates the important role of lncRNA in the regulation mechanism of ceRNA in gastric cancer,and demonstrates the regulatory function of DLEU2 and DDX11-AS1 in gastric cancer for the first time.2.Prediction and experimental verification of LINC00941 function in gastric cancerIn this article,gastric cancer gene expression data and clinical data were obtained from the TCGA database.Data processing and analysis showed that LINC00941 is a gastric cancerrelated,metastasis-related and survival-related lncRNA,and has the potential to become a biomarker for the diagnosis and prognosis of gastric cancer.Then,the relationship between the expression of LINC00941 and clinical data of gastric cancer was analyzed.The results showed that the expression of LINC00941 is closely related to the depth of tumor invasion and the distant metastasis of gastric cancer.Based on the Weighted Gene Co-expression Network Analysis(WGCNA)method,a co-expression module based on LINC00941 was identified.The results of functional enrichment analysis indicated that LINC00941 was involved in cell proliferation,cell migration,and tumor metastasis.In this article,the loss-of-function analysis revealed that silence of LINC00941 inhibits gastric cancer cells proliferation,migration,and invasion in vitro and modulates tumor growth in vivo.By detecting the expression level of EMT markers,the results indicate that LINC00941 may participate in the metastasis process of gastric cancer cells by affecting EMT.This article systematically integrates bioinformatics and biological experimental methods,and effectively predicts and demonstrates the important role of LINC00941 in the process of gastric cancer proliferation and metastasis.This article found that LINC00941 may be a potential biomarker for the diagnosis,prognosis,and treatment of gastric cancer.In summary,this article effectively integrated bioinformatics methods and biological experimental techniques,and the first prediction and biological experiments verify the regulatory functions of DLEU2,DDX11-AS1,and LINC00941 in gastric cancer.Through the above research work,this article defines an accurate experimental object for the in-depth study of gastric cancer-related lncRNA function and provides an effective and effective way to detect,reverse and terminate the occurrence and development of gastric cancer by detecting or regulating lncRNA.This article also provides a reference for research on other cancers and complex diseases.
Keywords/Search Tags:Gastric cancer, non-coding RNA, competing endogenous RNA, gene regulatory network, biomarker
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