Identification of RP11-770J1.4-CTXN1 as an immunomodulatory axis in Low-Grade Glioma

Abstract: Human gliomas are lethal brain cancers whose progression is complexly regulated. Emerging evidence reveals that long non-coding RNAs (lncRNAs), functioning as competing endogenous RNAs, participate in regulatory networks in tumors. Here, we comprehensively integrated and analyzed expression profiles for RNAs in low-grade glioma (LGG). Functional annotation analysis suggested that immune-related signature is involved in progression of glioma. Importantly, survival analysis showed that features in networks exhibited close relations to the prognosis. Further experiments showed that RP11-770J1.4 regulated the expression of CTXN1 by sponging hsa-miR-124-3p. Correlation analysis and GSEA enrichment revealed that RP11-770J1.4 is an immune-related lncRNA. Single cell RNA sequencing (scRNA-seq) combined with glioma stem cells (GSCs) model and patient samples revealed CTXN1 distributed mainly in tumor core, rather than periphery. Utilizing immunohistochemistry staining in low-grade glioma cases, CTXN1 negatively correlated to CD8⁺ T cells infiltration. Knocking down Ctxn1 in GL261 cell decreased tumor weight and prolong survival time in vivo, while increased tumor CD8⁺ T cells infiltration. These findings revealed RP11-770J1.4-CTXN1 as novel immune regulator axis in glioma and provided potential therapeutic targets for LGG treatment.