Abstract: Objective To investigate the role of arachidonic acid (AA) metabolism-related endoplasmic reticulum genes in the development of HCC in a mouse hepatocellular carcinoma (HCC) microenvironment. Methods The function of differentially expressed endoplasmic reticulum membrane genes (ADEGs) involved in AA metabolism was analyzed by RNA-seq and bioinformatics using AA metabolism-related genes as the background, tumor tissues and paracancer tissues of mice were collect as the sample materials, and the expression of ADEGs was verified by RT-qPCR. Results There was a total of 35 ADEGs in HCC (gene expression in per million per thousand transcripts in sequencing base sequencing contained in the base sequence fragment number (FPKM) ≥2 or ≤0.5, and false positive rate (FDR) was ≤0.05), they were involved in the two biological applications (BPs), five cellcomponents (CCs), nine molecular functions(MFs), a protein loci sequence characteristics (US) and six(KPs) signal channel. The function of these genes was mainly focused on the endoplasmic reticulum membrane, especially the effect of iron ion binding(IIB)on the epoxygenase P450 pathway (EPP). Further analysis revealed that ADEGs in IIB had extensive single nucleotide site variation (SNV) and insertion and deletion (INDEL) in the HCC microenvironment, and its occurrence frequency was positively correlated with gene expression (r=0.83). Conclusions ADEGs in HCC microenvironment may cause EPP abnormalities mainly through IIB in the endoplasmic reticulum, thus playing an important role in the development and progression of HCC, SNV and INDEL may be important ways to regulate gene expression.

Key words: hepatocellular carcinoma, endoplasmic reticulum membrane, iron ion bonding, epoxygenase P450 pathway