Ma Yuanming, Zhang Chunjun, Zhang Bo, Yu Haibo, Yu Qingsong
Department of General Surgery, Shengzhou People's Hospital, Branch of First Affiliated Hospital of Zhejiang University, Shengzhou, Zhejiang 312400, P.R. China.
Oncol Lett. 2019 Jan;17(1):388-397. doi: 10.3892/ol.2018.9606. Epub 2018 Oct 22.
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 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 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.
肝细胞癌(HCC)是一种异质性恶性肿瘤类型,治疗方法有限。此外,不适当的免疫治疗表明有必要了解HCC的潜在机制。本研究的目的是探讨一种新型环状RNA(circRNA),即AR抑制的PABPC1 91 bp环状RNA(CircARSP91)对自然杀伤(NK)细胞诱导的免疫监视的影响。进行细胞毒性试验以确定NK细胞对HCC细胞的细胞毒性。使用circRNA过表达的特异性质粒建立稳定细胞系。此外,对HCC患者的样本进行分析,以确定当前数据与临床情况数据之间的关联。CircARSP91可增加HCC细胞对NK细胞细胞毒性的敏感性。在筛选了多种可能影响NK细胞激活的因素后,确定这种表型可能是由HCC细胞中mRNA和蛋白质水平上上调UL16结合蛋白1(ULBP1)的表达引起的。此外,患者样本产生的数据显著支持CircARSP91与ULBP1之间的正相关。总之,CircARSP91可通过增强NK细胞的细胞毒性来增强先天免疫监视,这意味着circRNA可能在肿瘤免疫中发挥作用。