Objective To screen differentially expressed lncRNA and miRNA in colon cancer,and to explore their association with colon cancer prognosis and related biological functions.Meth-ods The lncRNA and miRNA expression profile data and clinical information of colon cancer pa-tients were collected from TCGA database,and R software was used to screen differentially ex-pressed lncRNAs and miRNAs;Single-factor Cox regression analysis was used to identify differ-entially expressed lncRNA and miRNA that were significantly associated with prognosis;the miRNet database was used to construct a prognostic-related lncRNA-miRNA network;mirPath v.3 software was used for functional enrichment analysis;R software was used to build a prog-nostic risk model and validate it.CCK-8 experiments,scratch experiments,flow cytometry,and qPCR were used to evaluate the effects of knocking down TSPEAR-AS2 on the proliferation,mi-gration,apoptosis and downstream miRNA expression of human colon cancer HCT116 cells.Re-sults 1823 differentially expressed lncRNAs and 524 differentially expressed miRNAs were iden-tified in colon cancer tissues;158 lncRNAs and 31 miRNAs were found to be associated with co-lon cancer prognosis;an lncRNA-miRNA network composed of 8 lncRNAs and 14 miRNAs was constructed;GO and KEGG enrichment analyses showed that the lncRNA-miRNA network was mainly involved in tumor-related biological functions and pathways;11 key genes that could effec-tively evaluate colon cancer prognostic characteristics were identified,the survival time of the high-risk group was significantly shorter than that of the low-risk group in the prognostic risk model constructed from these 11 key genes(P<0.001),and the AUCs for predicting the survival of 1,3,and 5 years were 0.70,0.74,and 0.71,respectively.Knocking down TSPEAR-AS2 inhibited the proliferation,migration,and promoted apoptosis of HCT116 cells,and down-regulated the ex-pression of hsa-mir-4731-5p and hsa-mir-342-3p.Conclusion successful screening of colon cancer-associated lncRNA-miRNA network and the prognostic risk model constructed therefrom can has good predictive efficacy.TSPEAR-AS2 could be involved in regulating the proliferation,migra-tion,apoptosis,and downstream miRNA expression of colon cancer cells.