Diagnostic Value Of LINC01106 In Colorectal Cancer And Mechanism Exploration Based On Bioinformatics

Backgroundand objectiveColorectal cancer（CRC）is one of the most common malignant tumors.In recent years,its incidence has risen to the third place of malignant tumors,and its mortality ranks thesecond,with an upward trend.Due to the lack of sensitive and specific markers for early diagnosis,many patients with colorectal cancer were diagnosed as advanced and had a poor prognosis.Presently,the role of non-coding RNA in colorectal cancer has been widely concerned,especially long-chain non-coding RNA（lncRNA）.Recently,competitive endogenous RNA（ceRNA）has become a hot spot in the research field of colorectal cancer.Studies have shown that lncRNA is involved in the progression of colorectal cancer through ceRNA.In this study,we aim to explorethe expression and mechanism of long-chain noncoding RNA LINC01106 in colorectal cancer,and provide a potential molecular marker for the diagnosis and targeted therapy of colorectal cancer.Methods1.Based on the sequencing results of 15 pairs of tissue samples in GEO database,bioinformatics analysis showed that lncRNA with different expression was analyzed.In addition,the correlation between the expression of LINC01106 in colorectal cancer and the prognosis and survival was explored through GEPIA database.Combined with literature reports,LINC01106 with significant difference was screened out.2.qRT-PCR was used to detect the expression level of LINC01106 in 30 pairs of cancer tissues and their corresponding normal mucosa tissues adjacent to cancer.The expression of LINC01106 in total RNA of 30 patients’plasma and 30 healthy controls was detected by qRT-PCR.3.The expression of LINC01106 in 82 pairs of tissue chips was detected by in situ hybridization.The correlation analysis of clinicopathological data was performed by univariate analysis,and Chi-square Fish was used to test accurately when it is necessary.4.The miRNA targeted by LINC01106 was obtained through DIANA,miRDB and Reg2.0 databases.Get the downstream target genes of miRNA through miRDB,miRTar Base and Targetsacn databases;TCGA-COAD and GEO database were used to analyze the correlation between its expression and prognosis,and Spearman test was used for correlation analysis.5.The statistics were analyzed by SPSS.21 software and plotted by Graph Pad Prism8.0 software.The qRT-PCR results were calculated by 2^-△△CT,and the results were expressed as mean standard deviation.Chi-square test was used for counting data,and t test was used for measuring data.The survival curve was drawn by Kaplan-Meier method and Log Rank test,and the diagnostic efficacy was evaluated by receiver operating characteristic（ROC）curve and area under the curve（AUC）.P<0.05 showed the results were statistically different.Results1.GEO database and GEPIA bioinformatics analysis showed that LINC01106was up-regulated in colon adenocarcinoma and rectal adenocarcinoma with statistical significance（P<0.05）,but there was no significant difference between gastric cancer and esophageal cancer.Survival analysis showed that the increased expression of LINC01106 was associated with poor prognosis of colorectal cancer patients.GO and KEGG analysis showed that LINC01106 was mainly involved in the formation of cytoskeleton and the adhesion of epithelial cells.2.The results of qRT-PCR showed that the expression of LINC01106 in colorectal cancer tissue was significantly higher than that in normal mucosa adjacent to cancer（P<0.05）.In addition,compared with healthy controls,the expression of LINC01106 in plasma of patients with colorectal cancer was significantly increased,with statistical significance（P<0.05）.3.The results of tissue microarray in situ hybridization showed that the expression of LINC01106 in colorectal cancer tissues was significantly higher than that in normal mucosa adjacent to colorectal cancer（P<0.01）.The analysis of clinical case data showed that the up-expression of LINC01106 was significantly correlated with tumor size（P<0.01）,but was not associated with age,sex,lymph node metastasis and distant metastasis.Kaplan-Meier survival analysis showed that high expression of LINC01106 was associated with poor prognosis of colorectal cancer.ROC curve was drawn.When sensitivity and specificity were 83.27%and 70.36%,the area under the curve was 73.83%,suggesting that LINC01106 can be used as a potential biomarker for CRC diagnosis.4.Nine miRNA targeted by LINC01106 were screened through database and bioinformatics prediction,among which miR-5698,miR-550a-5P and miR-4716-3p were down-regulated in colorectal cancer,and the low expression of miR-5698 was related to poor prognosis of colorectal cancer.A total of 96 miRNA target genes were screened from bioinformatics database,among which SUV39H1 and RAB15 were significantly up-regulated in colorectal cancer,and there was a significant positive correlation between SUV39H1 and LINC01106,whose high expression was not conducive to the survival and prognosis of colorectal cancer patients.ConclusionLINC01106 is up-regulated in colorectal cancer tissues and plasma,and is closely related to the malignant phenotype of colorectal cancer,which can be used as a potential molecular marker for the diagnosis of colorectal cancer.LINC01106/miR-5698/SUV39H1 may play an important role in the occurrence and development of colorectal cancer through ceRNA mechanism.