This study aimed to annotate the role of long intergenic non-coding RNA 152 (LINC00152) in CD8⁺ T cells mediated immune responses in gastric cancer (GC) and the underlying mechanism. LINC00152 expression levels were detected through RT-PCR. For tumor engraftment, HGC-27 cells that received LINC00152 shRNA, LINC00152 overexpression vectors, enhancer of zeste homolog 2 (EZH2) shRNA or combination transfection were injected into mice. Chromatin immunoprecipitation (ChIP) assay was used to explore the interaction between LINC00152, Cys-X-cys ligand 9 (CXCL9) and Cys-X-cys ligand 10 (CXCL10). Flow cytometry was adopted to measure the CD8⁺ T-cell infiltration in tumor issue. In this study, we found increased LINC00152 expression levels are positively associated with the poor prognosis of GC patients and negatively associated with the CD8 levels. ChIP assay verified that LINC00152 recruits EZH2 to the promoters of CXCL9 and CXCL10, thus the silencing of LINC00152 promoted the production of CXCL9 and CXCL10. Knockdown of LINC00152 suppressed tumor cells growth in vivo and in vitro, increased tumor-infiltrating CD8⁺ T cells numbers and promoted the expression of CXCL9, CXCL10 and C-X-C Motif Chemokine Receptor 3 (CXCR3) in xenograft tumors. While CD8⁺ T cell depletion reversed the tumor suppression effect of LINC00152 silence. Besides, the silencing of EZH2 partly inhibited the promotion effect LINC00152 on tumor growth. Our study indicated that LINC00152 inhibition suppressed the tumor progress may through promoting CD8⁺ T-cell infiltration.

本研究旨在解释长基因间非编码 RNA 152 (LINC00152) 在 CD8 ⁺ T 细胞介导的胃癌 (GC) 免疫反应中的作用及其潜在机制。通过 RT-PCR 检测 LINC00152 表达水平。对于肿瘤移植，将接受 LINC00152 shRNA、LINC00152 过表达载体、zeste 同源物 2 (EZH2) shRNA 增强子或组合转染的 HGC-27 细胞注射到小鼠体内。染色质免疫沉淀 (ChIP) 测定用于探索 LINC00152、Cys-X-cys 配体 9 (CXCL9) 和 Cys-X-cys 配体 10 (CXCL10) 之间的相互作用。采用流式细胞术测量 CD8 ⁺肿瘤问题中的 T 细胞浸润。在这项研究中，我们发现增加的 LINC00152 表达水平与 GC 患者的不良预后呈正相关，与 CD8 水平呈负相关。ChIP 检测证实 LINC00152 将 EZH2 募集到 CXCL9 和 CXCL10 的启动子，因此，LINC00152 的沉默促进了 CXCL9 和 CXCL10 的产生。敲除 LINC00152 可抑制体内和体外肿瘤细胞的生长，增加肿瘤浸润的 CD8 ⁺ T 细胞数量，并促进 CXCL9、CXCL10 和 CXC 基序趋化因子受体 3 (CXCR3) 在异种移植肿瘤中的表达。虽然 CD8 ⁺T 细胞耗竭逆转了 LINC00152 沉默的肿瘤抑制作用。此外，EZH2的沉默部分抑制了LINC00152对肿瘤生长的促进作用。我们的研究表明，LINC00152 抑制可能通过促进 CD8 ⁺ T 细胞浸润来抑制肿瘤进展。