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The Effect And Mechanism Of Long Non-coding RNA CASC19 Regulates HMGA2 Through MiR-491-5p In Gastric Cancer

Posted on:2022-12-21Degree:DoctorType:Dissertation
Country:ChinaCandidate:L X ZhangFull Text:PDF
GTID:1484306773954289Subject:Oncology
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Background and objective:Gastric cancer is a common malignant tumor,Long non-coding RNA(lncRNA)and micro RNA(miRNA)are important regulators that affect tumor proliferation,metastasis,and chemotherapy resistance,thereby participating in tumor progression.CASC19 is a new bio-marker which can promote tumor invasion and metastasis.However,the mechanism of CASC19 affecting the invasion and progression of gastric cancer through micro RNA is not clear.Therefore,this study aimed to explore the function of the CASC19/miR-491-5p/HMGA2 regulatory axis in gastric cancer.Method:1 The gastric cancer prognosis model in the TCGA database was constructed by the WGCNA method,in which CASC19 is included and the downstream miR-491-5p of CASC19 is screened through bioinformatics analysis to find the target gene HMGA2.2 To explore the expression and prognosis of CASC19 in gastric cancer through clinical samples,and investigate the effects of inhibiting CASC19 on the proliferation,migration,invasion and other functions of gastric cancer cells through CCK-8,EDU,Wound healing assay,Transwell,Western blot and flow cytometry experiments.3 The regulatory relationship between CASC19 and miR-491-5p was verified by dual luciferase assay and RT-PCR.The effect of miR-491-5p on the proliferation,apoptosis and EMT of gastric cancer cells was demonstrated by CCK-8,flow cytometry and Western blot.4 The regulatory relationship between HMGA2 and miR-491-5p was verified by dual-luciferase assay and RT-PCR.To search the functional impact of HMGA2 in gastric cancer by immunohistochemistry,CCK-8 and flow cytometry experiments.5 Whether CASC19 regulates the level of HMGA2 through miR-491-5p was verified through Dual-luciferase reporter gene assay and RT-PCR,and then CCK-8,Transwell,Wound healing assay,flow cytometry and animal experiments to further verify CASC19/miR-491-5p/HMGA2 regulatory axis.Result:1 The prognostic model of gastric cancer constructed by AC103702.2,CASC19 and PVT1 is relatively stable.Among them,CASC19 is an important indicator affecting the prognosis of gastric cancer patients and related to N stage.At the same time,CASC19/miR-491-5p/HMGA2 axis was predicted.2 The expression of CASC19 in gastric cancer tissues and gastric cancer cells is higher than that in normal tissues and gastric mucosal epithelial cells respectively.The expression level of CASC19 is related to the T stage,N stage,and tumor size of patients.Knockdown of the expression of CASC19 can inhibit the ability of proliferation,migration,invasion and EMT conversion of gastric cancer cells,inhibiting the expression of CASC19 can promote the apoptosis of gastric cancer cells.3 CASC19 can regulate the expression of miR-491-5p.Increasing the expression of miR-491-5p can inhibit the proliferation and EMT conversion of gastric cancer cells,and promote the apoptosis of gastric cancer cells,while decreasing the expression of miR-491-5p can promote the proliferation and EMT conversion and inhibit the apoptosis of gastric cancer cells.4 HMGA2 is the target gene of miR-491-5p.The expression of HMGA2 in gastric cancer tissues is higher than that in adjacent tissues.At the same time,the expression level of HMGA2 is related to the N and T stages of the patients.Reducing the level of HMGA2 can promote cell apoptosis and inhibit the proliferation of gastric cancer cells.5 Cell experiments and animal experiments proved that CASC19 can regulates the expression of HMGA2 through miR-491-5p,thereby affecting the biological functions of gastric cancer.Conclusion:CASC19,miR-491-5p and HMGA2 play important roles in gastric cancer,besides,CASC19 regulates the expression of HMGA2 through miR-491-5p to affect the development of gastric cancer.This axis has become an important marker and target for the diagnosis and treatment of gastric cancer.
Keywords/Search Tags:gastric cancer, CASC19, miR-491-5p, HMGA2
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