Correlation Between Non-coding RNA Gene Polymorphism And Risk Of Colorectal Cancer In Shannxi Han Nationalities And The Role Of MIR17HG And Its MicroRNAs In Colorectal Cancer

【Obiective】Screening the susceptible population of Han nationality colorectal cancer in Shaanxi by non-coding RNA gene polymorphism,screening microRNAs closely related to the occurrence of colorectal cancer,and discussing its role in the occurrence and development of colorectal cancer,for clinical prevention and early diagnosis Colorectal cancer provides a reference basis.【Methods】1.Design a controls,and case-control association study including 514 CRC patients and 510 healthy select 9 lnc RNAs genes [ MIR137 HG,MIR143HG(CARMN),MIR3142 HG,LINC-PINT,MIR124-1HG,MIR675HG(H19),MIR17HG,MIR497HG and MIR133A1 HG ],7 miRNAs genes(MIR577,MIR608,MIR675,MIR192,MIR618,MIR492 and MIR423)and49 SNPs of GREM1 gene,Agena Mass ARRAY genotyping was performed on the selected SNPs.Chi-square test and logistic regression with genetic model and stratification analysis were used to evaluate the relationship of these SNPs with the risk of CRC and its clinicopathological parameters in Han nationalities in Shaanxi,China,and perform haplotype analysis and MDR analysis to find the best model to predict the risk of CRC.2.Analyzed the expression of MIR17HG and miR-17-92 a clusters in the tissues and blood of CRC cases and control groups.Download tumor RNA-seq data from TCGA and GDC databases,and analyze the mRNA expression data of MIR17HG.Download survival data in the TCGA database for survival analysis,and miRNA-seq expression data for analysis of differences in different disease stages.Download data from SRA and GEO databases to compare the abundance of free miR-17-92 a clusters in serum of healthy people and patients with different cancer stages.3.Included 50 cases of Han nationality in Shaanxi that have not undergone any treatment and50 healthy controls.The expression of microRNAs in the miR-17-92 a cluster in their serum was detected by RT-qPCR,and the ROC curve was used to judge these microRNAs in the diagnosis of colorectal cancer cases.4.Used hsa-miR-18a-5p mimics and hsa-miR-18a-5p inhibitor to treat colorectal cancer HCT116 and SW480,and study the effect of hsa-miR-18a-5p on colorectal cancer cells.The shortest path algorithm was used to analyze the network relationship between each gene in the protein interaction network and the differentially expressed genes,and to screen the candidate key target genes for colorectal cancer and conduct preliminary verification.【Result】1.rs73376930 is associated with increasing the risk of CRC in the Han population in Shaanxi,China;while rs7549905,rs7318578,rs633727 and rs58658771 are associated with reducing the risk of CRC in the Han population in Shaanxi,China.Haplotype GA compared to CA(rs3024270 and rs2075744),haplotype CT compared to TA(rs4779584 and rs58658771),haplotype AA compared to AG(rs2293581 and rs73376930)were all associated with reducing the risk of CRC.The model with 5 SNPs(rs9440302,rs353300,rs1582417,rs157928,rs3024270)is the best model for predicting CRC,its cross-check consistency is 9/10,and the balance accuracy is 0.719,which can predict the risk of CRC OR It was 6.65(95% CI:4.96-8.91).2.MIR17HG is highly expressed in CRC tissues,the highest in stage IV cases and black people.The miR-17-92 a cluster is highly expressed in CRC tissues and serum,and hsa-miR-20a-5p has the highest expression.3.The relative expression levels of hsa-miR-18a-5p and has-miR-92a-1 in the serum of colorectal cancer cases of Han nationality in Shaanxi were higher than those of the normal population.The expression of hsa-miR-18a-5p is related to clinical stage.Used serum hsa-miR-18a-5p+CEA+AFP diagnosis of early colorectal cancer AUC=0.899(95% CI:P<0.001),sensitivity=0.88,specificity=0.738,whichis better than a single0.836-0.962,index.4.hsa-miR-18a-5p can reduce the proliferation and cloning ability of CRC cells,and increase the occurrence of cell apoptosis.The shortest distance algorithm was used to evaluate the 11 possible target genes of hsa-miR-18a-5p.hsa-miR-18a-5p can inhibit the development of CRC by targeting LIF.【Conclusions】1.Non-coding RNA gene polymorphisms Model with 5 SNPs can predict the risk of colorectal cancer.Model with 5 SNPs can predict the risk of CRC.2.MIR17HG is closely related to the occurrence of colorectal cancer.MIR17HG and its microRNAs are highly expressed in CRC tissues,and the amount of expression is related to clinical stage and ethnicity.The miR-17-92 a cluster is highly expressed in CRC serum.3.The expression of hsa-miR-18a-5p and hsa-miR-92a-3p increased in the serum of CRC of Han nationality in Shaanxi,hsa-miR-18a-5p+CEA+AFP has superiority in the diagnosis of early colorectal cancer.4.The high expression of hsa-miR-18a-5p can reduce the proliferation and cloning ability of colorectal cancer cells,and promote the occurrence of apoptosis.