circRNA of AR-suppressed PABPC1 91 bp enhances the cytotoxicity of natural killer cells against hepatocellular carcinoma via upregulating UL16 binding protein 1

AR 抑制的 PABPC1 91 bp 的 circRNA 通过上调 UL16 结合蛋白 1 增强自然杀伤细胞对肝细胞癌的细胞毒性

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作者:Yuanming Ma, Chunjun Zhang, Bo Zhang, Haibo Yu, Qingsong Yu

Abstract

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy type with limited approaches for treatment. Additionally, inappropriate immune therapy indicates that the understanding the underlying mechanism of HCC is necessary. The aim of the present study was to investigate the influence of a novel circular RNA (circRNA), circRNA of AR-suppressed PABPC1 91 bp (CircARSP91), on immune surveillance induced by natural killer (NK) cells. An in vitro cell cytotoxicity assay was performed to determine the cytotoxicity of NK cells against HCC cells. A specific plasmid for circRNA overexpression was used to establish stable cell lines. Additionally, samples from patients with HCC were analyzed to determine the association between the present in vitro data and those of clinical settings. CircARSP91 could increase the susceptibility of HCC cells to NK cell cytotoxicity. Following screening multiple factors that could influence the activation of NK cells, it was determined that such a phenotype may be caused by upregulating UL16 binding protein 1 (ULBP1) expression in HCC cells at the mRNA and protein levels. Additionally, the data generated from patient samples significantly support a positive association between CircARSP91 and ULBP1. In conclusion, CircARSP91 could enhance innate immune surveillance by strengthening the cytotoxicity of NK cells, implying that circRNA may serve a role in tumor immunity.

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