PVT1 通过调节 STAT1 和 CX3CL1 促进胶质母细胞瘤的增殖和巨噬细胞的免疫抑制极化。

AIMS: This study aimed to investigate the role of plasmacytoma variant translocation 1 (PVT1), a long non-coding RNA, in glioblastoma multiforme (GBM) and its impact on the tumor microenvironment (TME). METHODS: We assessed aberrant PVT1 expression in glioma tissues and its impact on GBM cell growth in vitro and in vivo. Additionally, we investigated PVT1's role in influencing glioma-associated macrophages. To understand PVT1's role in cell growth and the immunosuppressive TME, we performed a series of comprehensive experiments. RESULTS: PVT1 was overexpressed in GBM due to copy number amplification, correlating with poor prognosis. Elevated PVT1 promoted GBM cell proliferation, while its downregulation inhibited growth in vitro and in vivo. PVT1 inhibited type I interferon-stimulated genes (ISGs), with STAT1 as the central hub. PVT1 correlated with macrophage enrichment and regulated CX3CL1 expression, promoting recruitment and M2 phenotype polarization of macrophages. PVT1 localized to the cell nucleus and bound to DHX9, enriching at the promoter regions of STAT1 and CX3CL1, modulating ISGs and CX3CL1 expression. CONCLUSION: PVT1 plays a significant role in GBM, correlating with poor prognosis, promoting cell growth, and shaping an immunosuppressive TME via STAT1 and CX3CL1 regulation. Targeting PVT1 may hold therapeutic promise for GBM patients.

目的：本研究旨在探讨浆细胞瘤变异易位 1（PVT1）作为一种长链非编码 RNA 在多形性胶质母细胞瘤（GBM）中的作用及其对肿瘤微环境（TME）的影响。

方法：我们评估了异常 PVT1 在神经胶质瘤组织中的表达及其对体外和体内 GBM 细胞生长的影响。此外，我们研究了 PVT1 影响胶质瘤相关巨噬细胞的作用。为了了解 PVT1 在细胞生长和免疫抑制性 TME 中的作用，我们进行了一系列全面的实验。

结果：由于拷贝数扩增，PVT1 在 GBM 中过度表达，与预后不良相关。升高的 PVT1 促进了 GBM 细胞的增殖，而其下调则抑制了体外和体内的生长。PVT1 抑制了 I 型干扰素刺激基因（ISGs），STAT1 是其中心枢纽。PVT1 与巨噬细胞的富集相关，并调节 CX3CL1 的表达，促进巨噬细胞的募集和 M2 表型极化。PVT1 定位于细胞核，与 DHX9 结合，在 STAT1 和 CX3CL1 的启动子区域富集，调节 ISGs 和 CX3CL1 的表达。

结论：PVT1 在 GBM 中发挥重要作用，与预后不良相关，通过调节 STAT1 和 CX3CL1 促进细胞生长并塑造免疫抑制性 TME。针对 PVT1 可能为 GBM 患者提供治疗前景。