State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
Cancer Lett. 2023 Aug 10;569:216319. doi: 10.1016/j.canlet.2023.216319. Epub 2023 Jul 17.
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.
长链非编码 RNA（lncRNAs）已被报道参与多种生物学过程，包括肿瘤免疫。由于 lncRNAs 在细胞类型上具有高度特异性表达，因此在单细胞水平上研究 lncRNAs 将揭示 lncRNAs 的细胞类型特异性功能。然而，在单细胞水平上，lncRNA 在肿瘤免疫微环境（TIMEs）中的功能的泛癌症系统性单细胞分析仍然缺乏。在这里，我们对 TIMEs 中的 lncRNA 功能进行了泛癌症单细胞分析，并开发了一种工具 scLNC，专门用于在单细胞水平上进行 lncRNA 功能特征分析。scLNC 能够以细胞类型特异性的方式比较 lncRNA-mRNA 对、lncRNA 调控单元活性和单元功能水平的 lncRNA 功能。应用 scLNC，我们的分析描绘了 T 细胞亚群中跨肿瘤和肿瘤特异性的 lncRNA 调控谱，并揭示了 lncRNAs 在肿瘤浸润 T 细胞中建立的新调控单元，特别是在富含肿瘤的 T 细胞中。我们进一步通过它们的调控单元来描述 lncRNAs 的活性和功能变化。总的来说，我们的研究结果表明，lncRNAs 在富含肿瘤的 T 细胞中细胞因子产生、细胞激活和迁移的调控中发挥了重要作用，并进一步影响免疫治疗。
