| Background:Gastric cancer(GC)is one of the common malignant cancers in the world,and it is a serious threat to human health.According to the latest cancer statistics in 2018,globally,there were 18.1 million new cancer cases and 960 cancer deaths worldwide in 2018.Among these new cancer cases,gastric cancer was approximately 1.03 million,accounting for new cancers.5.7% of the cases,the sixth highest incidence;cancer deaths,gastric cancer deaths more than 780,000 deaths,accounting for 8.2% of cancer deaths,ranking second in all types of tumors.The pathogenesis of gastric cancer is very insidious.Its early stages are mostly asymptomatic or have only mild symptoms.Due to the lack of effective early screening methods,70% of patients are in the advanced stage at the time of diagnosis,and most have experienced tumor invasion and metastasis of varying degrees.Even with radical surgical resection,the prognosis of the patient is still poor.The 5-year survival rate in the current stage is about 30%,and the prognosis is worse with distant metastasis,and the median survival time is about 1 year.The occurrence of gastric cancer is the result of a combination of environmental and genetic factors.Environmental risk factors include dietary factors,occupational exposure,H.pylori infection,and smoking and drinking.Genetic factors play a critical role in the progress of gastric cancer.These studies mainly focus on key protein-coding genes,that is,mutations in key genes cause changes in their encoded proteins and cause abnormal biological functions.Abnormal genes and signaling pathways are involved in the development of gastric cancer.Long non-coding RNAs(IncRNAs)are a class of non-coding RNAs with transcription lengths greater than 200 nucleotides,located in the nucleus or cytoplasm.LncRNA is involved in many important biological regulatory processes.It can bidirectionally regulate the expression of protein-coding genes,and can both activate and inhibit.In recent decades,the dysregulation of lncRNA has been shown to be related to the occurrence and development of various human cancers including gastric cancer.Studies have shown that HULC and H19 are involved in the occurrence and development of gastric cancer.Therefore,understanding the role of lncRNA will help elucidate the potential biological functions of different cancers,including gastric cancer.MicroRNAs(miRNAs)is an important class of small endogenous non-coding RNA molecules,consisting of approximately 21-25 nucleotides.MiRNAs usually target one or more mRNAs,regulate gene expression by inhibiting translation or degradation of target mRNAs,affecting tumor cell invasion,proliferation,and protein synthesis.Increasing research shows that IncRNA-miRNA-mRNA network plays an important role in tumorigenesis and development.We use bioinformatics software to predict that lncRNARP11-169F17.1 in gastric cancer cells can specifically regulate the rise of miR-449 a expression to further regulate the expression of Notch 1 protein,thereby inhibiting the apoptosis of gastric cancer cells and promoting the development of gastric cancer.MiRNA-449 is a member of the miRNA family,which consists of miRNA-449 a,miRNA-449 b,and miRNA-449 c.Compared with miR-449 c,more studies have shown that the abnormal expression of miR-449a/b is closely related to the process of tumorigenesis and development.As a tumor suppressor,miRNA-449 induces cell cycle arrest,apoptosis,and inhibition of invasion by regulating key factors in cell cycle and apoptosis.Notch signaling pathway is widely expressed in human tissues and is involved in various pathophysiological processes such as central nervous system development,inflammatory response,and tumor progression.The changes in the expression of the signaling pathway receptors(Notch 1-4)and ligands(Jaggedl-2,DLLl,DLL3-4)are closely related to tumorigenesis and progression.Notch 1 is an important member of the Notch signaling pathway.Notchl causes tumor formation mainly by inducing the expression of growth-promoting genes such as cyclin D1 and C-myc and triggering anti-apoptotic pathways such as P13 kinase / AKT.In this study,bioinformatics analysis and some common molecular biology techniques were used to explore the effects and related mechanisms of long-chain non-coding lncRNA-RP11-169F17.1 and IncRNA-miRNA-mRNA networks on the biological effects of gastric cancer.Purpose:This study uses lncRNA-RP11-169F17.1 as the entry point to explore the biological function of lncRNA-RP11-169F17.1 in the development of gastric cancer and to screen lncRNA-RP11-169F17.1 for regulating the biological behavior of gastric cancer And explore the possible regulatory pathways of lncRNA-RP11-169F17.1.To provide powerful theoretical and experimental evidence for the diagnosis,treatment and prognosis of clinical gastric cancer Method:1.Detecting the expression level of lncRNA in gastric cancer tissues and adjacent normal tissues by bioinformatics technology,screening the lncRNA expression profiles of GC tissues,constructing a co-expression network,and selecting the target lncRNA in this expression profile result2.Real-time PCR was used to detect the expression differences in gastric cancer tissues and adjacent tissues,and to analyze the connection between the expression o f lncRNA-RP11-169F17.1 and the clinicopathological characteristics of gastric cancer patients;3.By constructing stably expressed gastric cancer cell lines with high and high expression of lncRNA-RP11-169F17.1 and low expression of lncRNA-RP11-169F17.1.Plate clones,Edu experiments,scratch tests,and Transwell tests were used to compare the proliferation,migration,and invasion capabilities of gastric cancer cell lines lncRNA-RP11-169F17.1 after intervention.4.Bioinformatics predicts that the key molecules of lncRNA-RP11-169F17.1-miR-449a-NOTCH1 are involved in the regulation of gastric cancer,and the regulation is verified by luciferase report experiments,RNA immunoprecipitation experiments,cell scratch experiments,and transwell experiments.Result1.The expression of lncRNA-RP11-169F17.1 in GC tissues is significantly higher than that in adjacent tissues,and the high expression of lncRNA-RP11-169F17.1 is related to TNM stage,tumor size,degree of differentiation,and the presence or absence of lymph node metastasis In addition,the high expression level of lncRNA-RP11-169F17.1 was significantly correlated with the overall survival and disease-free survival of patients with gastric cancer.2.LncRNA-RP11-169F17.1 knockdown inhibited the proliferation,migration and invasion of GC cells;lncRNA-RP11-169F17.1 overexpression improved the proliferation,migration and invasion of GC cells.3.lncRNA-RP11-169F17.1 is located in the cytoplasm;lncRNA-RP11-169F17.1 and NOTCH1 both have conserved miR-499 a binding sites;miR-449 a and lncRNA-RP11-169F17.1,miR-449 a and NOTCH1 can be targeted for binding;lncRNA-RP11-169F17.1 regulates the expression of NOTCH1 through miR-449 a and promotes gastric cancer migration and invasion.ConclusionLncRNA-RP11-169F17.1 can be used as miR-449 a ceRNA,which can competitively combine with it to up-regulate NOTCH1 expression,promote gastric cancer proliferation,migration and invasion,and inhibit tumor cell apoptosis.Therefore,studying the regulation of lncRNA-RP11-169F17.1-miR-449a-NOTCH1 is of great significance for optimizing clinical diagnosis and treatment and promoting the development of new targeted drugs. |
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