LncRNA PCBP1-AS1 correlated with the functional states of cancer cells and inhibited lung adenocarcinoma metastasis by suppressing the EMT progression

Abstract

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.