ABSTRACT
Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors, and lung adenocarcinoma (LUAD) accounts for up to 40% of NSCLC. Ring finger protein 213(RNF213) has been demonstrated to suppress several cancers, including glioblastoma and breast cancer. Nonetheless, the role of RNF213 in LUAD has not been investigated. The expression of RNF213 in LUAD tissues was analyzed by western blotting, The Cancer Genome Atlas, Genotype Tissue Expression Project, and Gene Expression Omnibus databases. Prognostic value analysis was performed through the Kaplan-Meier Plotter database. We determined the role of RNF213 in LUAD cells through cell counting kit8 assay, migration, and invasion assay. The clinical roles of RNF213 were evaluated by immunohistochemical staining assay (IHC) and Kaplan-Meier survival analysis. RNF213 expression was reduced in LUAD, thus affecting the prognosis of LUAD. And RNF213 could suppress the migration and invasion of LUAD cells to prevent tumor development. the expression of RNF213 is positively correlated with the overall survival, providing a novel marker in the prognosis of LUAD patients.
Subject(s)
Adenocarcinoma of Lung , Adenosine Triphosphatases , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Ubiquitin-Protein Ligases , Humans , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/pathology , Adenosine Triphosphatases/metabolism , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Transcription Factors , Ubiquitin-Protein Ligases/metabolismABSTRACT
INTRODUCTION: The underlying mechanisms of gastric cancer (GC) remain unknown. Therefore, in this study, we employed a comprehensive approach, combining computational and experimental methods, to identify potential key genes and unveil the underlying pathogenesis and prognosis of GC. METHODS: Gene expression profiles from GEO databases (GSE118916, GSE79973, and GSE29272) were analyzed to identify DEGs between GC and normal tissues. A PPI network was constructed using STRING and Cytoscape, followed by hub gene identification with CytoHubba. Investigations included expression and promoter methylation analysis, survival modeling, mutational and miRNA analysis, gene enrichment, drug prediction, and in vitro assays for cellular behaviors. RESULTS: A total of 83 DEGs were identified in the three datasets, comprising 41 up-regulated genes and 42 down-regulated genes. Utilizing the degree and MCC methods, we identified four hub genes that were hypomethylated and up-regulated: COL1A1, COL1A2, COL3A1, and FN1. Subsequent validation of their expression and promoter methylation on clinical GC samples through targeted bisulfite sequencing and RT-qPCR analysis further confirmed the hypomethylation and overexpression of these genes in local GC patients. Furthermore, it was observed that these hub genes regulate tumor proliferation and metastasis in in vivo and exhibited mutations in GC patients. CONCLUSION: We found four potential diagnostic and prognostic biomarkers, including COL1A1, COL1A2, COL3A1, and FN1 that may be involved in the occurrence and progression of GC.