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

川地163 巨噬细胞极化 肝细胞癌 基因沉默 M2巨噬细胞 癌症研究 小RNA 转染 巨噬细胞 活力测定 医学 生物 细胞 细胞培养 体外 基因 生物化学 遗传学
作者
Ming Yang,Tao Yu,Li Han
出处
期刊:Journal of Viral Hepatitis [Wiley]
卷期号:31 (4): 189-196 被引量:7
标识
DOI:10.1111/jvh.13917
摘要

Hepatocellular 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.
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