Hsa_circ_0010882 facilitates hepatocellular carcinoma progression by modulating M1/M2 macrophage polarization

Abstract

AbstractHepatocellular carcinoma (HCC) is one common malignant tumour with a high immunosuppressive tumour microenvironment and poor outcomes. This study investigated the influence of hsa_circ_0010882 on M1/M2 macrophage polarization in the progression of HCC. A total of 125 paired tissue specimens from HCC patients who underwent hepatectomy were collected. M1 and M2 phenotypes macrophages were induced using THP‐1. After co‐cultured with macrophages and transfected HCC cells, the viability, migration and invasion of HCC cells were detected by cellular experiments. Bioinformatic databases and dual‐luciferase reporter assays were used to predict and validate the interaction between circ_0010882 and miR‐382. Expression of circ_0010882 was increased in HCC tissues and associated with shorter overall survival outcomes. The mRNA expression of M2 macrophage markers Arg‐1, CD163 and CD206 were elevated in HCC tissues. Interfering with circ_0010882 increased M1‐type macrophage markers (TNF‐α and iNOS) while decreasing M2‐type macrophage markers (Arg‐1 and CD206). Silencing of circ_0010882 strengthened the capacity of M1 macrophages to suppress HCC cell viability, migration capacities and invasion potential while reducing the ability of M2 macrophages to promote above cellular abilities. MiR‐382 was a direct target miRNA of circ_0010882. The circ_0010882 expression was increased in HCC tissues and associated with poor prognosis of HCC patients. Silencing of circ_0010882 inhibits macrophage M2 polarization in HCC progression by regulating miR‐382 expression. Circ_0010882 may serve as a biomarker to provide novel strategies for the treatment of HCC and patient rehabilitation, thereby improving the prognosis of patients.