TM6SF2 E167K Variant Overexpression Promotes Expression of Inflammatory Cytokines in the HCC Cell Line HEPA 1-6.

Background and Aims: Accumulated evidence has shown that chronic liver inflammation is one of the main risks of hepatocellular carcinoma (HCC), and E167K variant of the transmembrane 6 superfamily member 2 (TM6SF2) plays an important role in the progression of chronic liver diseases and HCC. The aim of this study was to explore effects of the TM6SF2 E167K variant on expression of the inflammatory cytokines TNF-alpha, IL-2, IL-6 and IL-8 in the HCC cell line HEPA 1-6. Methods: HEPA 1-6 cells were infected with lentivirus containing either the TM6SF2 E167K variant or TM6SF2 wildtype, or control plasmids. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were conducted to analyze the expression of the inflammatory cytokines TNF-alpha, IL-2, IL-6 and IL-8. A t-test was used for statistical analysis. Results: Compared with the control group and TM6SF2 overexpression group, the relative expression of IL-2 and IL-6 mRNAs were significantly elevated in the TM6SF2 E167K overexpression group (p < 0.05). The relative mRNA expression of IL-8 in the TM6SF2 and TM6SF2 E167K overexpression groups were increased compared to the control group (p < 0.05). No obvious differences were observed for the expression of TNF-alpha in each group. The expression of TNF-alpha, IL-2, IL-6 and IL-8 that was tested by western blotting showed the same trends as the qRT-PCR results. Conclusions: In conclusion, the E167K variant of the TM6SF2 gene could promote the expression of inflammatory cytokines IL-2 and IL-6 in HEPA 1-6 cells, suggesting that the TM6SF2 E167K variant may accelerate the progression of HCC.