Molecular Virology and Immunology Research Group, Atta-Ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
Department of Surgery, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.
Mol Biol Rep. 2023 Jul;50(7):5957-5967. doi: 10.1007/s11033-023-08542-x. Epub 2023 Jun 2.
Interleukin-22 (IL-22) is a pro-inflammatory cytokine released during the immune response in chronic liver injury. Although IL-22 mediates tissue regeneration, its uncontrolled production may generate a carcinogenic environment resulting in hepatocellular carcinoma (HCC). This study aims to identify the effect of IL-22 on anti-apoptotic and metastatic genes and the molecular pathways responsible for IL-22-mediated hepatic carcinogenesis.
Three cancerous liver lines, HepG2, SNU-387, Huh7, and one normal liver line, THLE2, were treated with IL-22. RT-qPCR analysis was conducted to study the role of IL-22 in altering the expression levels of anti-apoptotic genes, MCL-1 and BCL-2, and metastatic genes, MMP-7 and MMP-9. A significant increase in expression levels of these genes was observed after IL-22 treatment. Furthermore, to explore the major pathways involved in IL-22-mediated upregulation of anti-apoptotic and metastatic genes, cells were treated with inhibitors of JAK/STAT and PI3K/AKT pathways along with IL-22. Resultantly, a significant decrease in expression levels of target genes was observed, indicating the involvement of JAK/STAT and PI3K/AKT signaling cascades in IL-22-mediated oncogenesis. Finally, Cell Scratch assay was performed to check the effect of IL-22 and inhibitors of JAK/STAT and PI3K/AKT on the metastatic potential of liver cells. While migration was observed in Huh7 and THLE2 cells treated with IL-22, no migration was observed in cells treated with IL-22 along with JAK/STAT and PI3K/AKT inhibitors. Results indicate that IL-22 encourages metastasis in HCC cells via the JAK/STAT and PI3K/AKT pathways.
Results showed that IL-22 upregulates anti-apoptotic and metastatic genes in HCC through JAK/STAT and PI3K/AKT signaling pathways.
白细胞介素-22（IL-22）是一种在慢性肝损伤的免疫反应中释放的促炎细胞因子。虽然 IL-22 介导组织再生，但它的不受控制的产生可能会产生致癌环境，导致肝细胞癌（HCC）。本研究旨在确定 IL-22 对抗凋亡和转移基因的影响，以及负责 IL-22 介导的肝致癌作用的分子途径。
用 IL-22 处理三种肝癌细胞系 HepG2、SNU-387、Huh7 和一种正常肝系 THLE2。进行 RT-qPCR 分析以研究 IL-22 改变抗凋亡基因 MCL-1 和 BCL-2 以及转移基因 MMP-7 和 MMP-9 的表达水平的作用。在用 IL-22 处理后，观察到这些基因的表达水平显著增加。此外，为了探讨参与 IL-22 介导的抗凋亡和转移基因上调的主要途径，用 JAK/STAT 和 PI3K/AKT 途径抑制剂和 IL-22 处理细胞。结果表明，观察到靶基因的表达水平显著降低，表明 JAK/STAT 和 PI3K/AKT 信号级联在 IL-22 介导的致癌作用中起作用。最后，进行细胞划痕试验以检查 IL-22 和 JAK/STAT 和 PI3K/AKT 抑制剂对肝细胞转移潜力的影响。在用 IL-22 处理的 Huh7 和 THLE2 细胞中观察到迁移，而在用 IL-22 加 JAK/STAT 和 PI3K/AKT 抑制剂处理的细胞中未观察到迁移。结果表明，IL-22 通过 JAK/STAT 和 PI3K/AKT 途径促进 HCC 细胞的转移。
结果表明，IL-22 通过 JAK/STAT 和 PI3K/AKT 信号通路在上皮性 HCC 中上调抗凋亡和转移基因。
