The development of single-cell RNA sequencing (scRNA-seq) provided us an unprecedented chance to identify novel oncogenes or tumor suppressors at single-cell resolution. Long non-coding RNAs (lncRNAs) related to the functional states of cancer cells might play vital roles in the progression of lung adenocarcinoma (LUAD). In this study, lncRNAs that were associated with the functional states of LUAD cells identified in scRNA-seq studies were screened based on the CancerSEA database. Differential gene expression analysis and survival analysis were performed in TCGA, GEO and our JSPH databases. Finally, transwell and tail vein metastasis assays were used to reveal the functions of our identified novel prognostic lncRNAs. A total of 849 lncRNAs were initially identified. Among them, 11 lncRNAs were found significantly associated with LUAD prognosis in the TCGA database. Two of them (PCBP1-AS1 and ZSCAN16-AS1) were further validated in independent GEO datasets. ScRNA-seq analysis showed that PCBP1-AS1 and ZSCAN16-AS1 were significantly negatively correlated with most of the functional states of LUAD cells, especially with metastasis. Functionally, PCBP1-AS1 was aberrantly downregulated in LUAD cells and tumor tissues. Knockdown of PCBP1-AS1 significantly promoted the migration and invasion of LUAD cells. Consistently, PCBP1-AS1 overexpression suppressed the metastasis of LUAD in vitro and in vivo. Besides, PCBP1-AS1 inhibition induced decreased E-cadherin expression and increased N-cadherin, Vimentin and Snail expression. In conclusion, PCBP1-AS1 could suppress the metastasis of LUAD by targeting the epithelial-mesenchymal transition pathway and might serve as a prognostic biomarker and a potential therapeutic target of LUAD.

中文翻译：

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LncRNA PCBP1-AS1与癌细胞的功能状态相关，并通过抑制EMT进展来抑制肺腺癌转移。

单细胞 RNA 测序 (scRNA-seq) 的发展为我们提供了前所未有的机会，可以在单细胞分辨率下识别新的致癌基因或肿瘤抑制基因。与癌细胞功能状态相关的长链非编码 RNA (lncRNAs) 可能在肺腺癌 (LUAD) 的进展中发挥重要作用。在本研究中，基于 CancerSEA 数据库筛选了与 scRNA-seq 研究中鉴定的 LUAD 细胞功能状态相关的 lncRNA。在 TCGA、GEO 和我们的 JSPH 数据库中进行了差异基因表达分析和生存分析。最后，使用 transwell 和尾静脉转移测定来揭示我们鉴定的新型预后 lncRNA 的功能。最初共鉴定了 849 个 lncRNA。他们之中，在 TCGA 数据库中发现 11 个 lncRNA 与 LUAD 预后显着相关。其中两个（PCBP1-AS1 和 ZSCAN16-AS1）在独立的 GEO 数据集中得到进一步验证。ScRNA-seq 分析表明 PCBP1-AS1 和 ZSCAN16-AS1 与 LUAD 细胞的大多数功能状态显着负相关，尤其是与转移。在功能上，PCBP1-AS1 在 LUAD 细胞和肿瘤组织中异常下调。PCBP1-AS1 的敲低显着促进了 LUAD 细胞的迁移和侵袭。一致地，PCBP1-AS1 过表达抑制了 LUAD 在体外和体内的转移。此外，PCBP1-AS1 抑制诱导 E-cadherin 表达降低，N-cadherin、波形蛋白和 Snail 表达增加。综上所述，