Pan-glioma analyses reveal species- and tumor-specific regulation of neuron-glioma synapse genes by lncRNAs

Abstract

Gliomas are highly heterogeneous and aggressive. Malignant cells in gliomas can contact normal neurons through a synapse-like structure (called neuron-to-glioma synapse, NGS) to promote their proliferation, but it is unclear whether NGS gene expression and regulation show species- and tumor-specificity. This question is important in that many anti-cancer drugs are developed upon mouse models. To address this question, we conducted a pan-glioma analysis using nine scRNA-seq datasets from humans and mice. We also experimentally validated the key element of our methods and verified a key result using TCGA datasets of the same glioma types. Our analyses revealed that NGS gene expression and regulation by lncRNAs are highly species- and tumor-specific. Importantly, simian-specific lncRNAs are more involved in NGS gene regulation than lncRNAs conserved in mammals, and transgenic mouse gliomas have little in common with PDX mouse models and human gliomas in terms of NGS gene regulation. The analyses suggest that simian-specific lncRNAs are a new and rich class of potential targets for tumor-specific glioma treatment, and provide pertinent data for further experimentally and clinically exmining the targets.