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The Mechanism Of LncRNA SNHG6 Promoting Glycolysis In Colorectal Cancer By Regulating DLD By HnRNPA1

Posted on:2024-01-17Degree:MasterType:Thesis
Country:ChinaCandidate:Z Y DingFull Text:PDF
GTID:2544306926469334Subject:Internal medicine (digestive diseases)
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Background and purposeGlobally,the third most common malignancy is colorectal cancer,which seriously endangers public safety.More importantly,the mortality rate remains high,in second place[1].In recent years,it is one of the hot issues in basic tumor research that malignant tumors promote their malignant behavior by adjusting metabolic pathways,and has become a hallmark of tumors,especially glycolytic function[2].How do tumors regulate their unique glycolytic function?Clarifying its mechanism of action will be of great help to our understanding of colorectal cancer and can help us find new treatments.lncRNAs are RNAs that are more than 200 units long and do not translate into proteins.LncRNA can promote tumor multiplication,enhance its invasion and migration ability,and regulate the drug resistance mechanism of tumors[3].LncRNA can not only affect the function of miRNAs by binding to miRNAs,but also by binding to proteins to affect the expression of downstream molecules.Intranuclear heterogeneous ribosotins can perform their biological functions by interacting with RNA[4].In CRC,LncRNA can influence the expression of downstream molecules by binding to intranuclear heterogeneous ribososins,thereby promoting the the proliferation and metastasis of CRC[5,6].DLD is a protein-coding gene involved in glucose metabolism,pyruvate metabolism,and citric acid cycling,and it is an enzyme that produces reactive oxygen species and participates in redox activity,which promotes tumor aerobic glycolysis[7-9].Therefore,in this study,we want to explore the specific mechanism of lncRNA regulating glycolytic function in colorectal cancer.Methods1.Analyze the expression levels of lncRNA SNHG6 using online website.1)Oncomine and literature review verified the expression levels of lncRNA SNHG6 in various tumors;2)Validation of lncRNA SNHG6 expression levels in different colorectal cancer types by GEPIA and Starbasev3.0.2.Analysis of sequencing results and basic experiments were used to verify that lncRNA SNHG6 participates in the glycolytic function of colorectal cancer cells.1)By analyzing the sequencing results by using data analysis methods such as KEGG,GSEA,and WGCNA,lncRNA SNHG6 is involved in metabolic pathways,especially glycolytic metabolic pathways,in colorectal cancer;2)Glucose uptake and lactic acid production by colorectal cancer cells were measured by glucose uptake kit and lactate production kit after changing the expression of lncRNA SNHG6.3.lncRNA SNHG6 affects glycolytic function in colorectal cancer cells via DLD.1)Through the sequencing results,the relevant genes in the glycolysis pathway in different analysis methods were extracted,and the key downstream molecule DLD was obtained by intersection,and the expression of DLD was verified;2)LncRNA SNHG6 can regulate the expression of DLD which was verified by RT-qPCR and western blot,and the glycolytic function of DLD in colorectal cancer can be verified by lactic acid kit;3)Verification by lactic acid kit that lncRNA SNHG6 affects glycolytic function in colorectal cancer through DLD.4.lncRNA SNHG6 enhances DLD expression by competitively binding to hnRNPA1 proteins.1)The inverse correlation between hnRNPA1 and DLD was verified by qRT-PCR and western Blot;2)The binding of hnRNPA1 protein and lncRNA SNHG6 and DLD mRNA was verified by RIP,and the colorectal cancer cells that stably interfered with lncRNA SNHG6 were transfected into the siRNA of hnRNPA1,and then further verified by qRT-PCR and western Blot experiments that the downregulation of DLD caused by interference with lncRNA SNHG6 was hnRNPA1 dependent.Results1.Compared to normal tissue,LncRNA SNHG6 is highly expressed in colorectal cancer;2.Colorectal cancer cells that stably interfered with lncRNA SNHG6 decreased the function of aerobic glycolysis;3.lncRNA SNHG6 affects glycolytic function in colorectal cancer cells via DLD;4.lncRNA SNHG6 promotes DLD expression by competitively binding hnRNPA1,thereby promoting glycolytic function in colorectal cancer cells.ConclusionThis study found that LncRNA SNHG6 was highly expressed in colorectal cancer compared with normal tissues.lncRNA SNHG6 promotes DLD expression by competitively binding hnRNPA1,thereby promoting glycolytic function in colorectal cancer cells.
Keywords/Search Tags:Colorectal cancer, Glycolysis, LncRNA SNHG6, HnRNPA1, DLD
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