Upregulated microRNA‐132 in T helper 17 cells activates hepatic stellate cells to promote hepatocellular carcinoma cell migration in vitro

Abstract

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.

Kidney microRNA Expression Pattern in Type 2 Diabetic Nephropathy in BTBR Ob/Ob Mice

“…Apart from immune diseases, the relation between miRNAs and Th17 has been demonstrated in other pathologies. In hepatocellular carcinoma–derived Th17 cells, a recent article showed increased miR-132 levels, another upregulated miRNA in our study, and demonstrated that the use of a miR-132 mimic accelerates Th17 differentiation in vitro ( Feng et al, 2021 ). At the kidney level, there are few studies on the role of miRNAs in Th17 differentiation ( Lavoz et al, 2020a ).…”

Novel Risk Classification Based on Pyroptosis-Related Genes Defines Immune Microenvironment and Pharmaceutical Landscape for Hepatocellular Carcinoma

“…Th17 cells were reported to inhibit growth and metastasis via the stimulation of cytotoxic T cells and natural killer cells within the TME [ 55 ]. In the HCC microenvironment, Th17 cells have a non-pathogenic phenotype and produce anti-inflammatory cytokines [ 56 , 57 , 58 ]. Classical M1 macrophages engage the inflammatory response and anti-tumor immunity, while alternative M2 macrophages are defined by their anti-inflammatory properties in the immunosuppressive microenvironment [ 58 ].…”

“…In the HCC microenvironment, Th17 cells have a non-pathogenic phenotype and produce anti-inflammatory cytokines [ 56 , 57 , 58 ]. Classical M1 macrophages engage the inflammatory response and anti-tumor immunity, while alternative M2 macrophages are defined by their anti-inflammatory properties in the immunosuppressive microenvironment [ 58 ]. Previous studies have shown that, due to the role of tumor-associated macrophages in immune invasion, higher levels of tumor-activated macrophages are positively associated with poor prognosis in HCC patients [ 49 , 59 ].…”

The Mechanism Underlying the ncRNA Dysregulation Pattern in Hepatocellular Carcinoma and Its Tumor Microenvironment

“…Some studies have also explored the function of miRNAs in Th17 cells in the TME of HCC. During Th17 cell differentiation, treatment with the miR-132 mimic promoted the differentiation of Th17 cells, leading to a higher percentage of Th17+ cells and higher secretion of IL-17 and IL-22 ( 97 ). Furthermore, miR-132-overexpressing Th17 cells could enhance the activation of hepatic stellate cells (HSCs), inducing HCC cell EMT and migration ( 97 ).…”