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| Hsa_circ_0044556 Mediates the Killing of Hepatocellular Carcinoma Cells by NK Cells via miR145/PD-L1 |
| ZHENG Wen, LI Meng, ZHANG Yanli, et al |
| Shandong Provincial Third Hospital, Shandong Jinan 250031, China |
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Abstract Objective: To investigate the role of hsa_circ_0044556 in the immune escape of hepatocellular carcinoma cells and its related mechanisms. Methods: Tumor tissues and their paraneoplastic tissues from hepatocellular carcinoma patients were collected to detect hsa_circ_0044556 and PD-L1 expression levels by qRT-PCR and correlation analysis were performed. The expression levels of hsa_circ_0044556 and PD-L1 in normal hepatic epithelial HL-02 cells and hepatocellular carcinoma SMMC-7721 and HCCLM3 cells were detected by qRT-PCR. The targeting relationship between hsa_circ_0044556 and miR145 and miR145 and PD-L1 was examined by informatics prediction and luciferase reporter assay. The si-hsa_circ_0044556, si-miR145 and si-NC were transfected into HCCLM3 cells by liposome transfection method, grouped as: si-NC group, si-hsa_circ_0044556 group, si-miR145 group and si-hsa_circ_0044556 + si-miR145 group. The expression level of PD-L1 and cell proliferation ability was compared among the groups. The sensitivity to NK cell killing was tested by NK cell toxicity assay. Results: The expression levels of hsa_circ_0044556 and PD-L1 were elevated in tumor tissues compared with paraneoplastic tissues (P<0.05), and hsa_circ_0044556 was positively correlated with PD-L1 expression (r=0.5481). In HL-02, SMMC-7721, and HCCLM3 cells, hsa_circ_0044556, and PD-L1 expression levels were sequentially increased (P<0.05). Hsa_circ_0044556 was targeted to inhibit miR145 expression; miR145 was targeted to inhibit PD-L1 expression. Compared with the si-NC group, the si-hsa_circ_0044556 group showed elevated miR145 gene expression, decreased PD-L1 protein expression, diminished cell proliferation, and increased sensitivity to NK cell killing (P<0.05); compared with the si-NC group, the si-miR145 group had elevated PD-L1 gene and protein expression, increased cell proliferation capacity and decreased sensitivity to NK cell killing (P<0.05); compared with the si-hsa_circ_0044556 group, the si-hsa_circ_0044556 + si-miR145 group had PD-L1 expression level increased, cell proliferation capacity increased, and sensitivity to NK cell killing decreased (P<0.05). Conclusion: In hepatocellular carcinoma cells, hsa_circ_0044556 mediates immune escape of tumor cells by promoting the proliferation of hepatocellular carcinoma cells through the miR145/PD-L1 signaling axis while inhibiting sensitivity to NK cell killing.
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2022, Vol. 28 
