Abstract: Objective To analyze the expression level of m6A reader insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in hepatocellular carcinoma (HCC) and its impact on the prognosis of HCC patients, and explore the role of IGF2BP1 in hepatocellular carcinoma and its underlying mechanism. Methods The mRNA-seq data of 5 pairs of HCC sample and the data from TCGA-LIHC were used to identify the expression of IGF2BP1 in HCC, and the clinical follow-up data of 343 HCC patients in the TCGA database was used to analyze the effect of IGF2BP1 expression on the overall survival of HCC patients. The TCGA database was used to screen the co-expressed mRNA of IGF2BP1, and the m6Avar website was used to predict the m6A locus of mRNA and its RNA binding protein and other information, and finally constructed the gene regulatory network of IGF2BP1. Results IGF2BP1 gene was up-regulated in HCC (log2FC RNA-seq of HCC=10.684, P<0.001;log2FC TCGA-LIHC =7.032, P<0.001). The median survival time of HCC patients with low IGF2BP1 was 5.84 years, while that of patients with high expression was 4.44 years(P=0.011). The 22 differentially expressed mRNAs had a targeted binding relationship with IGF2BP1, and were positively correlated with its expression level. Among them, 15 highly expressed mRNAs such as HMGA2 could shorten the overall survival of HCC patients. In addition, the potential m6A methylation sites of HMGA2, PEG10, CEP55, RHO, CDC6 and KIF23 genes were located in their 3′-UTR miRNA-binding sites. Conclusions IGF2BP1 is highly expressed in HCC and results in shorter overall survival. IGF2BP1 may up-regulate mRNA expression through m6A methylation and miRNA inhibition, thereby promoting the occurrence of HCC and leading to poor prognosis.

Key words: Hepatocellular carcinoma, m6A, IGF2BP1, Gene regulatory network, Prognosis