LncRNA HCG18影响鼻咽癌细胞PD-L1表达及CD8<sup>+</sup>T细胞的杀伤功能研究

doi:10.3969/j.issn.1006-6233.2024.07.03

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Abstract Objective: To investigate the regulatory mechanism of LncRNA HCG18 on the function of CD8⁺ T cells against nasopharyngeal carcinoma (NPC) cells. Methods: The expression of HCG18 in NPC tissues and paracancerous tissues was detected by qRT-PCR. The expression of HCG18 in human nasal mucosal epithelial cells (HNEpC) and NPC cell lines (CNE1, CNE2, HONE-1, HNE-2) was also detected. CNE1 cells were divided into si-HCG18 group, si-NC group, and si-HCG18⁺PD-L1 group; HNE-2 cells were divided into HCG18 group, Vector group, and HCG18⁺sh-PD-L1 group. CNE1 and HNE-2 cells in each group were co-cultured with CD8⁺ T cells for 24 h (si-HCG18+CD8⁺T group, si-NC+CD8⁺T group, si-HCG18+PD-L1+CD8⁺T group, HCG18+CD8⁺T group, Vector+CD8⁺T group, and HCG18+sh-PD-L1+CD8⁺T group). The concentrations of INF-γ, TNF-α, and IL-2 in the co-culture system were detected by enzyme-linked immunosorbent assay (ELISA), and the tumor cell lysis rate was detected by a cytotoxicity assay kit. Western blot was used to detect PD-L1 protein expression. Dual luciferase reporter gene assay was used to verify the targeting relationship between HCG18 and miR-20b-5p, and the targeting relationship between miR-20b-5p and PD-L1. Results: The expression of HCG18 in NPC tissues was significantly higher than that in paracancerous tissues, and the expression of HCG18 in CNE1, CNE2, HONE-1, and HNE-2 cells was significantly higher than that in HNEpC cells (P<0.05). The expression of PD-L1 in CNE1 cells of the si-HCG18 group was significantly lower than that in the si-NC group (P<0.05), and the expression of PD-L1 in HNE-2 cells of the HCG18 group was significantly higher than that in the Vector group (P<0.05). Compared with the si-NC+CD8⁺T group, the concentrations of INF-γ, TNF-α, and IL-2 in the co-culture system of the si-HCG18+CD8⁺T group were significantly increased (P<0.05), and the CNE1 cell lysis rate was significantly increased (P<0.05). Compared with the si-HCG18+CD8⁺T group, the concentrations of INF-γ, TNF-α, and IL-2 in the co-culture system of the si-HCG18+PD-L1+CD8⁺T group were significantly decreased (P<0.05), and the CNE1 cell lysis rate was significantly decreased (P<0.05). Compared with the Vector+CD8⁺T group, the concentrations of INF-γ, TNF-α, and IL-2 in the co-culture system of the HCG18+CD8⁺T group were significantly decreased (P<0.05), and the HNE-2 cell lysis rate was significantly decreased (P<0.05). Compared with the HCG18+CD8⁺T group, the concentrations of INF-γ, TNF-α, and IL-2 in the co-culture system of the HCG18+sh-PD-L1+CD8⁺T group were significantly increased (P<0.05), and the HNE-2 cell lysis rate was significantly increased (P<0.05). miR-20b-5p is a target gene of HCG18, and PD-L1 is a target gene of miR-20b-5p. Conclusion: HCG18 upregulates PD-L1 expression in NPC cells and suppresses the anti-tumor activity of CD8⁺ T cells.

Key words： Nasopharyngeal carcinoma HCG18 PD-L1 CD8+T cells

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.07.03 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I7/1068

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