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Downregulation of hsa_circ_0074854 Suppresses the Migration and Invasion in Hepatocellular Carcinoma via Interacting with HuR and via Suppressing Exosomes-Mediated Macrophage M2 Polarization

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单位: [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pediat Surg, Union Hosp, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China [2]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Rheumatol & Immunol, Wuhan 430030, Hubei, Peoples R China [3]Wuhan Univ, Dept Thyroid & Breast Surg, Zhongnan Hosp, Wuhan 430071, Hubei, Peoples R China
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关键词: circular RNAs hepatocellular carcinoma exosomes macrophage polarization invasion

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Background: Circular RNAs (circRNAs) have been identified as key factors in the development of hepatocellular carcinoma (HCC). However, the role and potential molecular mechanism of circRNAs in HCC remain largely unclear. In addition, exosomes are known as important messengers of the cross-talk between tumor cells and immune cells, while the role of extracellular circRNAs in the cell-to-cell communication of tumor cells and immune cells remains not unclear. Methods: The level of hsa_circ_0074854 in HCC cell lines and HCC cell-derived exosomes was assessed using RT-qPCR assay. In addition, CCK-8 and transwell assays were used to determine the viability, migration and invasion of HCC cells. Results: Hsa_circ_0074854 expression was upregulated in HCC tissues and HCC cell lines. Additionally, hsa_circ_0074854 knockdown was found to inhibit HCC growth in vitro and in vivo. Mechanistically, hsa_circ_0074854 knockdown inhibited the migration and invasion of HCC cells via interacting with human antigen R (HuR) to reduce its stability. Furthermore, hsa_circ_0074854 can be transferred from HCC cells to macrophages via exosomes. Exosomes with downregulated hsa_circ_0074854 suppressed macrophage M2 polarization, which in turn suppressing migration and invasion of HCC cells both in vitro and in vivo. Conclusion: Downregulation of hsa_circ_0074854 suppresses the migration and invasion in hepatocellular carcinoma via interacting with HuR and via suppressing exosomes-mediated macrophage M2 polarization. Collectively, these findings may help to understand the diagnosis and treatment of HCC.

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出版当年[2020]版:
大类 | 2 区 医学
小类 | 2 区 药学 3 区 纳米科技
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 药学 3 区 纳米科技
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出版当年[2019]版:
Q1 PHARMACOLOGY & PHARMACY Q2 NANOSCIENCE & NANOTECHNOLOGY
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Q1 PHARMACOLOGY & PHARMACY Q2 NANOSCIENCE & NANOTECHNOLOGY

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第一作者单位: [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pediat Surg, Union Hosp, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China
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