Pan-cancer survey of lncRNA rewiring and functional alternation in tumor-infiltrating T cell by scLNC

作者：Lei Yang, Qianqian Meng, Fang Hong, Mengyu Zhao, Xin Gao · 发表于：Cancer Letters · 年份：2023 · DOI：10.1016/j.canlet.2023.216319 · 被引用次数：4 · 研究领域：Cancer-related molecular mechanisms research、RNA modifications and cancer、Mycobacterium research and diagnosis

Long non-coding RNAs (lncRNAs) have been reported to involve in diverse biological processes, including tumor immunity. Since lncRNAs are expressed with high cell-type specificity, investigation of lncRNAs at the single-cell level will unveil the cell-type-specific functions of lncRNAs. However, at the single-cell level, a systematic pan-cancer analysis of lncRNA functions in tumor immune microenvironments (TIMEs) remains lacking. Here, we performed pan-cancer single-cell profiling of lncRNA functions in TIMEs and developed a tool, scLNC, tailored for lncRNA functional characterization at the single-cell level. scLNC enabled the comparison of lncRNA function from the levels of lncRNA-mRNA pairs, lncRNA regulatory unit activity and unit function in a cell-type-specific manner. Applying scLNC, our analysis depicted the cross-tumor and tumor-specific lncRNA regulatory profiles in the T cell subtypes and revealed the new regulatory units that lncRNAs established in tumor-infiltrating T cells, particularly in the tumor-enriched T cells. We further characterized the activity and functional alternations of lncRNAs through their regulatory units. Overall, our findings suggested that lncRNAs played an important role in the regulation of cytokine production, cell activation and migration in tumor-enriched T cells and further in immunotherapy.