锌指蛋白503反义RNA2（ZNF503-AS2）是一个很有前景的治疗靶点，且与胶质瘤中的免疫微环境相关。

ZNF503-AS2 is a promising therapeutic target and is associated with the immune microenvironment in glioma.

作者信息

Wu Yibo, Mu Guangjing, Li Fang, Sun Yanfei, Lin Xiaoying, Liu Xuemeng, Zhao Zhimin, Han Mingzhi, Wang Donghai, Huang Bin, Li Xingang

机构信息

Department of Neurosurgery, Jinan Microecological Biomedicine Shandong Laboratory and Shandong Key Laboratory of Brain Function Remodeling, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Qilu Hospital, Shandong University, Jinan, China.

Shandong Key Laboratory of Brain Function Remodelling, Jinan, China.

出版信息

PLoS One. 2024 Dec 2;19(12):e0314618. doi: 10.1371/journal.pone.0314618. eCollection 2024.

DOI:10.1371/journal.pone.0314618

PMID:39621695

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11611154/

Abstract

BACKGROUND

Glioma is the most common intracranial malignancy, and the available treatment options are poor. Long noncoding RNAs (lncRNAs) have been reported to be involved in the malignant progression of glioma. The role of ZNF503-AS2 in glioma has not been reported.

METHODS

We screened ZNF503-AS2 with upregulated expression in glioblastoma (GBM) by analyzing the TCGA, CGGA and GTEx databases. Single sample gene set enrichment analysis (ssGSEA) was used to calculate the enrichment of immune cells and signaling pathways in glioma samples. Single-cell datasets were used to analyze the distribution of ZNF503-AS2. In vitro experiments were used to investigate the biological function of ZNF503-AS2.

RESULTS

ZNF503-AS2 was highly expressed in glioma and was associated with poor prognosis, malignant progression and infiltration of immunosuppressive cells. Single-cell transcriptomic analysis showed that ZNF503-AS2 was mainly expressed in macrophages and tumor cells. Further analysis revealed that immunotherapy may have better efficacy in patients with low ZNF503-AS2 expression. In vitro experiments showed that knockdown of ZNF503-AS2 reduced the proliferation, invasion and migration ability of glioma cells, induced G2/M cell cycle arrest and promoted apoptosis.

CONCLUSIONS

ZNF503-AS2 might be a valuable biomarker for predicting the prognosis of glioma patients and a potential target for glioma therapy.

摘要

背景

胶质瘤是最常见的颅内恶性肿瘤，现有的治疗选择效果不佳。据报道，长链非编码RNA（lncRNA）参与胶质瘤的恶性进展。ZNF503-AS2在胶质瘤中的作用尚未见报道。

方法

我们通过分析TCGA、CGGA和GTEx数据库，筛选出在胶质母细胞瘤（GBM）中表达上调的ZNF503-AS2。采用单样本基因集富集分析（ssGSEA）计算胶质瘤样本中免疫细胞和信号通路的富集情况。利用单细胞数据集分析ZNF503-AS2的分布。通过体外实验研究ZNF503-AS2的生物学功能。

结果

ZNF503-AS2在胶质瘤中高表达，与预后不良、恶性进展及免疫抑制细胞浸润相关。单细胞转录组分析表明，ZNF503-AS2主要在巨噬细胞和肿瘤细胞中表达。进一步分析显示，ZNF503-AS2表达低的患者接受免疫治疗可能疗效更好。体外实验表明，敲低ZNF503-AS2可降低胶质瘤细胞的增殖、侵袭和迁移能力，诱导G2/M期细胞周期阻滞并促进细胞凋亡。