Single-cell Analysis of Long Non-coding RNAs (lncRNAs) in Tumor-Associated Macrophages (TAMs) in the Glioblastoma Microenvironment

Abstract

Glioblastoma (GBM) is the most severe type of brain tumor with poor prognosis and low survival rate, characterized by molecular heterogeneity and immunosuppressive microenvironment which pose a

significant challenge in improving treatment strategies. It is found that the abundance of tumor- associated macrophages (TAMs) in the GBM microenvironment contributes significantly to tumor

progression, yet the understanding of the underlying mechanism remains limited. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancer biology, including their involvement in tumor progression mechanisms mediated by TAMs. In this research, we performed single-cell RNA sequencing analysis on 17,803 cells from 6 glioma patient samples to profile the GBM tumor microenvironment landscape. We identified five TAM subtypes distinguished by unique gene expression profiles, and highlighted the two primary TAM ontogenies: brain-resident microglia and

infiltrating monocyte-derived macrophages. Our analysis revealed PCED1B antisense RNA 1 (PCED1B- AS1) as a significantly expressed lncRNA in TAMs, particularly associated with immune-related

pathways. The enrichment of PCED1B-AS1 showed a context-dependent impact on prognosis across different TAM clusters, suggesting its role in regulating immune cell functions. We demonstrated that PCED1B-AS1 potentially plays a crucial role in GBM microenvironment through its interaction with TAMs. Our findings suggest that targeting PCED1B-AS1 could offer a novel therapeutic strategy for GBM. The use of scRNA-seq was pivotal in uncovering the heterogeneity of TAMs and the specific roles of lncRNAs within the tumor microenvironment.