Transcriptome changes in ERGIC3-knockdown hepatocellular carcinoma cells: ERGIC3 is a novel immune function related gene.

ABSTRACT

Objective: The expression of ERGIC3 is increased in a variety of tumors and promotes the growth and metastasis of liver cancer, but the molecular mechanism needs to be further studied.In this study, we aimed to analyze the molecular mechanism of ERGIC3 regulating the proliferation of human hepatocellular carcinoma (HCC) SMMC-7721 cells using transcriptomics. Methods: ERGIC3 was knocked down in SMMC-7721 cells by RNAi technique, and the expression of ERGIC3 was detected by Q-RT-PCR and Western Blot. RNA sequencing was performed in the Illumina HiSeq platform in the control group and the ERGIC3i group and bioinformatics methods were selected to analyze the data. Results: The expression of ERGIC3 was reduced to 10% in SMMC-7721 cells by RNAi technique, and 176 genes were up-regulated and 34 genes were down-regulated in ERGIC3i group compared with the control group. Analysis of the pathways and biological processes that enrich the function of differentially expressed genes showed thatthese differentially expressed genes were mainly involved in vesicular transport, growth factors, PI3K-Akt, NOD-like, Jak-STAT, NF-kappa B and other protein kinase-coupled receptors mediated signal transduction pathways, tumor immune response, collagen-integrin receptor-actin axis, and miRNA pathways. More importantly, most of the significantly altered pathways were related to immunity. ERGIC3 may be a key immune-related gene. Conclusion: Based on the transcriptomic analysis, the mechanism of ERGIC3 promoting the growth of HCC is link with the transport of growth factor receptor, cytokine receptor and collagen. Then it is involved in signal transduction pathways mediated by protein kinase-coupled receptors, PI3K-Akt, NOD-like, Jak-STAT and NF-kappa B. In particular, the mechanism is also involved in the ERGIC3-dependent immune pathways. ERGIC3 is a potential target for prevention and treatment of HCC.