MiR‐155 regulates M2 polarization of hepatitis B virus‐infected tumour‐associated macrophages which in turn regulates the malignant progression of hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC) initiated by hepatitis B virus (HBV) infection is a complicated process. MiR‐155 can alter the immune microenvironment to affect the host's anti‐infective ability. This study investigated the mechanism by which miR‐155 affects tumour‐associated macrophage (TAM) polarization at a molecular level, thus affecting the malignant progression of HBV + HCC. MiR‐155 and TAM‐related cytokine expression were analysed by qRT‐PCR. The distribution of TAMs was detected by immunohistochemistry. The effect of the aberrant miR‐155 expression on macrophage polarization was examined by flow cytometry. The targeted relationship was verified by dual‐luciferase assay, and the protein level of src homology 2 domain‐containing inositol polyphosphate 5‐phosphatase 1 (SHIP1) was detected by western blot. The proliferation of HCC cells was examined by CCK‐8 and colony formation assays. Invasion and migration of HCC cells were detected by transwell assay. In HBV + HCC tissues, miR‐155 was significantly highly expressed and the number of CD206‐positive TAM (CD206 + TAM) and CD68‐positive TAM (CD68 + TAM) were higher than those in HBV − HCC tissues. In addition, miR‐155 overexpression significantly promoted M2‐type macrophage polarization, whilst miR‐155 silencing expression significantly promoted M1‐type macrophage polarization. Besides, the miR‐155/SHIP1 axis accelerated HCC cell invasion, proliferation and migration by inducing M2‐type macrophage polarization. MiR‐155 accelerates HCC cell proliferation, migration and invasion by targeting SHIP1 expression and inducing macrophage M2 polarization. This finding provides new insights into the development of novel therapeutic strategies for combatting HBV + HCC and a new reference for exploring anti‐tumour immunotherapy.