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.

RARRES2 is involved in the “lock-and-key” interactions between osteosarcoma stem cells and tumor-associated macrophages

“…In addition, TAMs are involved in crosstalk with CSCs in various types of tumors 61 . M2-type TAMs promote cancer stem-like properties in tumors, including hepatocellular carcinoma 62 , breast cancer 63 , non-small cell lung cancer 64 , pancreatic ductal adenocarcinoma 65 , and glioblastoma multiforme 66 . Mitchum et al showed that ablation of CCR2 or CSF-1R signaling significantly blocked TAM infiltration in pancreatic ductal adenocarcinoma (PDAC), reduced the number of CD44 + ALDH1 + CSCs, and improved the response to chemotherapy 67 .…”

Tumor-Associated Macrophages (TAMs) Polarization by Single-Cell Sequencing Combined with Bulk Data in Hepatocellular Carcinoma Cell

“…The use of bioinformatics to search for potential therapeutic targets that can be used in the treatment of liver cancer is of great significance. Liver cancer is one of the most common malignancies in China, ranking 4th among new cancer cases and second among cancer deaths according to data on malignancies released by the National Cancer Center [22][23][24]. Cancer has become a serious threat to human health, and there are varying degrees of morbidity due to cancer around the world [25].…”

Effect of urokinase-type plasminogen activator combined with clinical stage and Barcelona Clinic Liver Cancer stage on the prognosis of patients with hepatocellular carcinoma

“…Moreover, PLAU also had certain positive correlations with the immune checkpoint-associated molecules CTLA4, PDCD1, and CD274. Previous studies have also shown that immune cells play an important role in the biological events of LIHC, such as miR-155 regulating M2 polarization of tumor associated macrophages infected with hepatitis B virus, thereby regulating the malignant progression of hepatocellular carcinoma ( 20 ). CD8 + CD226 high T cells in liver metastasis determine the prognosis of colorectal cancer patients receiving chemotherapy and radical surgery treatment ( 21 ).…”