Study on the role of circularCUX1 in the mechanism of drug resistance mediated by programmed death factor 1 ligand in hepatocellular carcinoma cells
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摘要: 目的 探究circularCUX1(circCUX1)对肝癌细胞免疫逃逸的作用及其相关机制。方法 收集45例肝癌切除肿瘤组织，qRT-PCR检测肿瘤组织程序性死亡因子1配体(PD-L1)的表达水平，circRNA-seq分析PD-L1高表达和低表达肿瘤组织中circRNA的差异表达，并比较circCUX1与PD-L1表达的相关性。在细胞实验中采用qRT-PCR和Western blot检测HCCLM3、HepG2、SMMC-7721细胞circCUX1和PD-L1的表达水平，通过NK细胞毒性实验检测对NK细胞的敏感性。将HCCLM3细胞分为si-NC组(转染si-NC)和si-circCUX1组(转染si-circCUX1)，检测两组细胞circCUX1和PD-L1的表达水平以及对NK细胞的敏感性。结果 在肝癌患者肿瘤组织中，与PD-L1低表达肿瘤组织比较，PD-L1高表达肿瘤组织有282个circRNA表达上调，307个circRNA表达下调，其中circCUX1与PD-L1的表达水平呈正相关(R=0.628 9，P< 0.05)。与HepG2细胞和SMMC-7721细胞比较，HCCLM3细胞中circCUX1的表达水平升高(P< 0.05)，PD-L1 mRNA和蛋白的表达水平升高(P< 0.05)，其对NK细胞的敏感性降低(P< 0.05)。与si-NC组比较，circCUX1组circCUX1的表达水平降低(P< 0.05)，PD-L1 mRNA和蛋白的表达水平降低(P< 0.05)，其对NK细胞的敏感性增加(P< 0.05)。结论 在肝癌组织中circCUX1与PD-L1的表达呈正相关，circCUX1通过影响PD-L1表达介导肝癌细胞的免疫逃逸。
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关键词:
- 肝细胞癌 /
- 环状RNA /
- 程序性死亡因子1配体 /
- 免疫逃逸 /
- 耐药
Abstract: Objective To explore the effect of circularCUX1(circCUX1) on the immune escape of hepatocellular carcinoma cells and its related mechanism.Methods Forty-five cases of hepatocellular carcinoma resected tumor tissues were collected, and the expression level of programmed death factor 1 ligand (PD-L1) in tumor tissues was detected by qRT-PCR. circRNA-seq was used to analyze the circRNA expression difference between the high and low expression of PD-L1, and the correlation between circCUX1 and PD-L1 expression was compared. In cell experiments, the expression levels of circCUX1 and PD-L1 in HCCLM3, HepG2 and SMMC-7721 cells were detected by qRT-PCR and Western blot, and the sensitivity to NK cells was detected by NK cell toxicity assay. HCCLM3 cells were divided into si-NC group(transfected with si-NC) and si-circCUX1 group(transfected with si-circCUX1), and the expression levels of circCUX1 and PD-L1 and their sensitivity to NK cells were detected.Results In tumor tissues of hepatocellular carcinoma patients, compared with tumor tissues with low PD-L1 expression, 282 circRNA with high PD-L1 expression were up-regulated and 307 circRNA were down-regulated, among which circCUX1 was positively correlated with PD-L1 expression level(R=0.628 9,P< 0.05). Compared with HepG2 cells and SMMC-7721 cells, the expression level of circCUX1 and the mRNA and protein expression of PD-L1 in HCCLM3 cells increased(P< 0.05), the sensitivity of HCCLM3 cells to NK cells decreased(P< 0.05). Compared with si-NC group, circCUX1 group had lower circCUX1 expression(P< 0.05), lower PD-L1 mRNA and protein expression(P< 0.05), and higher sensitivity to NK cells(P< 0.05).Conclusion circCUX1 is positively correlated with the expression of PD-L1 in hepatocellular carcinoma cells, and circCUX1 mediates the immune escape of HCC cells by affecting the expression of PD-L1. -
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