The contribution of miR-122 to the innate immunity by regulating toll-like receptor 4 in hepatoma cells

作者：Liyu Shi, Xiaoqiu Zheng, Yuzhuo Fan, Xiaolan Yang, Aimei Li, Jun Qian · 发表于：BMC Gastroenterology · 年份：2019 · DOI：10.1186/s12876-019-1048-3 · 被引用次数：31 · 研究领域：MicroRNA in disease regulation、Immune Response and Inflammation、Immune cells in cancer

BACKGROUND: Hepatocellular carcinoma (HCC) is a kind of malignancies to impact human health. It has been reported that aberrant toll-like receptor (TLR) signaling may contribute to the development and progression of HCC, especially TLR4. MiR-122, which extensively involved in hepatitis virus infection and the apoptosis of hepatoma cells, might be decreased in HCC patients livers. The hypothesis of this study was whether miR-122 plays a role in inflammatory pathways through regulating TLR4 expression in hepatoma cells. METHODS: The expression of miR-122 in the tissues of HCC patients compared to controls in TCGA datasets was analyzed. The relationship between miR-122 and TLR4 was detected in HCC cell lines by increasing/decreasing miR-122 expression. The target of miR-122 on TLR4 was confirmed by luciferase reporter assays. The proliferation of HCC cells and production of proinflammatory cytokines were measured with miR-122 upregulation and inhibition. RESULTS: We found that the expression of miR-122 was decreased in HCC tissues and showed the diagnostic capacity for HCC in TCGA datasets. MiR-122 and TLR4 expression have negative correlation in normal liver cells and HCC cells. Upregulation of miR-122 significantly inhibited TLR4 expression in hepatoma cells, including in hepatoma cells with the induction of LPS, while knocking down miR-122 increased TLR4 expression. By screening potential miR-122 targets among TLR4, we found that there was a putative miR-122 target in TLR4 3'...