RESUMEN
BACKGROUND: Cystatins are a class of proteins that can inhibit cysteine protease and are widely distributed in human bodily fluids and secretions. Cystatin SN (CST1), a member of the CST superfamily, is abnormally expressed in a variety of tumors. However, its effect on the occurrence and development of lung adenocarcinoma (LUAD) remains unclear. METHODS: We obtained transcriptome analysis data of CST1 from The Cancer Genome Atlas (TCGA) and GSE31210 databases. The association of CST1 expression with prognosis, gene mutations and tumor immune microenvironment was analyzed using public databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed to investigate the potential mechanisms of CST1. RESULTS: In this study, we found that CST1 was highly expressed in lung adenocarcinoma and was associated with prognosis and tumor immune microenvironment. Genetic mutations of CST1 were shown to be related to disease-free survival (DFS) by using the c-BioPortal tool. Potential proteins binding to CST1 were identified by constructing a protein-protein interaction (PPI) network. Gene set enrichment analysis (GSEA) of CST1 revealed that CST1 was notably enriched in epithelial-mesenchymal transition (EMT). Cell experiments confirmed that overexpression of CST1 promoted lung adenocarcinoma cells migration and invasion, while knockdown of CST1 significantly inhibited lung adenocarcinoma cells migration and invasion. CONCLUSIONS: Our comprehensive bioinformatics analyses revealed that CST1 may be a novel prognostic biomarker in LUAD. Experiments confirmed that CST1 promotes epithelial-mesenchymal transition in LUAD cells. These findings will help to better understand the distinct role of CST1 in LUAD.
Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Biomarcadores , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Pronóstico , Cistatinas Salivales/genética , Cistatinas Salivales/metabolismo , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: Lung cancer is the leading cause of cancer deaths worldwide. Long non-coding RNAs (lncRNAs) affect a series of cellular biological processes, including oncogene function promotion. In this study, we explored the functions and mechanisms of FAM83A antisense RNA 1 (FAM83A-AS1) in non-small cell lung cancer (NSCLC) progression. METHODS: The expression of FAM83A-AS1and FAM83A mRNA was analyzed using the Cancer Genome Atlas (TCGA) data. Proliferation, migration, invasion and Western blotting were measured after treatment with overexpressed or knockdown FAM83A-AS1. To determine the relationship between FAM83A-AS1 and FAM83A, RNase protection assay (RPA), amanitin treatment, RNA pulldown assay and RNA immunoprecipitation (RIP) assay were performed. RESULTS: High expression of FAM83A-AS1 in lung adenocarcinoma (LUAD) was closely associated with low overall survival (OS) and progression-free survival (PFS). Functionally, high FAM83A-AS1 expression increased LUAD cell proliferation and metastasis, indicating that FAM83A-AS1 exerted its oncogenic functions. Furthermore, FAM83A-AS1 promoted NSCLC progression via ERK signaling pathways. Mechanistically, FAM83A-AS1 post-transcriptionally increased FAM83A expression by enhancing pre-mRNA stability. FAM83A-AS1 enhanced FAM83A mRNA stability not only by forming an RNA duplex but also by binding to FBL. CONCLUSIONS: We determined that FAM83A-AS1 increased FAM83A expression by enhancing FAM83A pre-mRNA stability and promoted the tumorigenesis of LUAD.