MicroRNAs play an important role in the modulation of the immune system. T helper 17 (Th17) cells are involved in the modulation of the tumour microenvironment. However, the function of miRNA in Th17 cells in the tumour microenvironment is unclear. In this study, we analysed miR‐132 expression in Th17 cells and assessed the function of miR‐132 on Th17 cell differentiation. In addition, the effect of miR‐132 on Th17 cells in the tumour microenvironment, especially hepatic stellate cells (HSCs), was confirmed. CD4⁺ IL‐17 ∓ cells were isolated from hepatocellular carcinoma (HCC) tumour tissues. The expression of miR‐132 was higher in CD4⁺ IL‐17 + cells than in CD4⁺ IL‐17‐ cells. Human primary CD4⁺ T cells were used for Th17 cell differentiation. Compared with primary CD4⁺ T cells, Th17 cells expressed high levels of miR‐132. During Th17 cell differentiation, a miR‐132 mimic and inhibition were applied. After treatment with the miR‐132 mimic, the differentiation of Th17 cells accelerated, showing a a higher percentage of Th17 cells and the expression and secretion of IL‐17 and IL‐22. Smad nuclear interacting protein 1 (SNIP1), as one of the targets of miR‐132, decreased during Th17 cell differentiation–related Th17 differentiation and IL‐17 expression. The conditioned medium of miR‐132–overexpressing Th17 cells could increase the activation of the HSCs, which strongly promoted HCC cell migration and epithelial‐mesenchymal transition (EMT). In summary, miR‐132 positively regulates Th17 cell differentiation and improves the function of Th17 on HSCs for their tumour‐promoting effects.

中文翻译：

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T辅助细胞17中上调的microRNA-132激活肝星状细胞促进肝细胞癌细胞体外迁移


MicroRNA 在免疫系统的调节中发挥着重要作用。辅助 T 17 (Th17) 细胞参与肿瘤微环境的调节。然而，miRNA在肿瘤微环境中Th17细胞中的功能尚不清楚。在本研究中，我们分析了 Th17 细胞中 miR-132 的表达，并评估了 miR-132 对 Th17 细胞分化的功能。此外，还证实了miR-132对肿瘤微环境中的Th17细胞，尤其是肝星状细胞（HSC）的影响。从肝细胞癌 (HCC) 肿瘤组织中分离出 CD4 ⁺ IL-17 ∓ 细胞。 miR-132 在 CD4 ⁺ IL-17 + 细胞中的表达高于 CD4 ⁺ IL-17- 细胞。人原代CD4 ⁺ T细胞用于Th17细胞分化。与原代CD4 ⁺ T细胞相比，Th17细胞表达高水平的miR-132。在 Th17 细胞分化过程中，应用了 miR-132 模拟物和抑制作用。用miR-132模拟物处理后，Th17细胞的分化加速，显示出更高的Th17细胞百分比以及IL-17和IL-22的表达和分泌。 Smad 核相互作用蛋白 1 (SNIP1) 作为 miR-132 的靶标之一，在 Th17 细胞分化相关的 Th17 分化和 IL-17 表达过程中下降。 miR-132过表达Th17细胞的条件培养基可以增加HSC的活化，从而强烈促进HCC细胞迁移和上皮间质转化（EMT）。总之，miR-132 正向调节 Th17 细胞分化，并改善 Th17 对 HSC 的功能，从而发挥促肿瘤作用。