Identification of a PLCE1-regulated competing endogenous RNA regulatory network for esophageal squamous cell carcinoma

Abstract

Phospholipase C epsilon 1 (PLCE1) and the competing endogenous RNA (ceRNA) network are crucial for tumorigenesis and the progression of esophageal squamous cell carcinoma (ESCC). However, whether PLCE1 can regulate the ceRNA network in ESCC has not been clarified. In the present study, we aimed to identify the PLCE1-regulated ceRNA network and further elucidate the regulatory mechanisms by which ESCC is promoted. Microarray analysis was used to identify differentially expressed lncRNAs (DELs) and differentially expressed genes (DEGs) from three pairs of samples of PLCE-silenced Eca109 and control Eca109 cells. Next, the ceRNA regulatory network was established and visualized in Cytoscape, and functional enrichment analysis was performed to analyze DEGs from ceRNAs. Protein-protein interaction (PPI) networks among the DEGs were established by the STRING database to screen hub genes. Kaplan-Meier survival analysis was used to validate hub genes. Finally, PLCE1-related hub gene/lncRNA/miRNA axes were also constructed based on the ceRNA network. A total of 105 DELs and 346 DEGs were found to be dysregulated in the microarray data (|log2FC| >1.5, adjusted P<0.05). We constructed a PLCE1-regulated ceRNA network that incorporated 12 lncRNAs, 43 miRNAs, and 169 mRNAs. Functional enrichment analysis indicated that the DEGs might be associated with ESCC onset and development. A PPI network was established, and 9 hub genes [WD and tetratricopeptide repeats 1 (WDTC1), heat shock protein family A (Hsp70) member 5 (HSPA5), N-ethylmaleimide sensitive factor, vesicle fusing ATPase (NSF), fibroblast growth factor 2 (FGF2), cyclin dependent kinase inhibitor 1A (CDKN1A or P21), bone morphogenetic protein 2 (BMP2), complement C3 (C3), GM2 ganglioside activator (GM2A) and discs large MAGUK scaffold protein 4 (DLG4)] were determined from the network. Kaplan-Meier survival analysis validated four hub genes (BMP2, CDKN1A, GM2A, and DLG4) that were treated as prognostic factors. Ultimately, hub gene/lncRNA/miRNA subnetworks were obtained based on the 4 hub genes, 13 DEmiRNAs, and 10 DELs. In conclusion, the PLCE1-regulated ceRNA contributes to the onset and progression of ESCC and the underlying molecular mechanisms may provide insights into personalized prognosis and new therapies for ESCC patients.