Abstract
Esophageal squamous cell carcinoma (ESCC) is a 5-year survival rate unsatisfied malignancies. The study aimed to identify the novel diagnostic and prognostic targets for ESCC. Expression profiling (GSE89102, GSE97051, and GSE59973) data were downloaded from the GEO database. Then, differentially expressed (DE) lncRNAs, DEmiRNAs, and genes (DEGs) with P-values < 0.05, and |log2FC| ≥ 2, were identified using GEO2R. Functional enrichment analysis of miRNA-related mRNAs and lncRNA co-expressed mRNA was performed. LncRNA–miRNA–mRNA, protein–protein interaction of miRNA-related mRNAs and DEGs, co-expression, and transcription factors-hub genes network were constructed. The transcriptional data, the diagnostic and prognostic value of hub genes were estimated with ONCOMINE, receiver operating characteristic (ROC) analyses, and Kaplan–Meier plotter, respectively. Also, the expressions of hub genes were assessed through qPCR and Western blot assays. The CDK1, VEGFA, PRDM10, RUNX1, CDK6, HSP90AA1, MYC, EGR1, and SOX2 used as hub genes. And among them, PRDM10, RUNX1, and CDK6 predicted worse overall survival (OS) in ESCC patients. Our results showed that the hub genes were significantly up-regulated in ESCA primary tumor tissues and cell lines, and exhibited excellent diagnostic efficiency. These results suggest that the hub genes may server as potential targets for the diagnosis and treatment of ESCC.
Highlights
Esophageal cancer (EC) is the eight commonest type of worldwide cancer and the sixth leading gastrointestinal malignancy with a poor survival rate [1], which is caused by many factors, such as tobacco smoking, heavy drinking, lack of fruits and vegetables, and there are two main histological types of EC: esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) [2]
Abnormal expression of miRNA has been verified to be tightly associated with long non-coding RNAs (lncRNAs) and transcription factors (TFs), and accumulating researches have indicated that lncRNAs can act as ceRNAs by binding and sequestering the 3 -untranslated region (UTR) of messenger RNAs to regulate the mRNA and protein expression of target genes [9,10]. lncRNAs and miRNAs are becoming new kinds of diagnostic molecular markers of ESCC, and Chang et al reported that lncRNA TUSC7 suppressed chemotherapy resistance of ESCC by down-regulating miR-224 to adjust DESC1/EGFR/AKT pathway [11]
GEO2R, an interactive web tool that reprocessed the raw data in a Gene Expression Omnibus (GEO) series, allowing users to evaluate the distribution of the values for the samples have been selected and viewed graphically as a box plot, was employed to identify DElncRNAs, differentially expressed miRNA (DEmiRNA) and differentially expressed gene (DEG) by comparing ESCC and normal tissue samples
Summary
Esophageal cancer (EC) is the eight commonest type of worldwide cancer and the sixth leading gastrointestinal malignancy with a poor survival rate [1], which is caused by many factors, such as tobacco smoking, heavy drinking, lack of fruits and vegetables, and there are two main histological types of EC: esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) [2]. Abnormal expression of miRNA has been verified to be tightly associated with lncRNAs and transcription factors (TFs), and accumulating researches have indicated that lncRNAs can act as ceRNAs by binding and sequestering the 3 -untranslated region (UTR) of messenger RNAs (mRNAs) to regulate the mRNA and protein expression of target genes [9,10]. LncRNAs and miRNAs are becoming new kinds of diagnostic molecular markers of ESCC, and Chang et al reported that lncRNA TUSC7 suppressed chemotherapy resistance of ESCC by down-regulating miR-224 to adjust DESC1/EGFR/AKT pathway [11]. TFs are as significant factors involved in controlling transcription and post-transcriptional regulation of genes through binding to particular DNA sequences, and involves in proliferation, apoptosis, and migration of tumor cells. Further study is required to elucidate the interrelationships of lncRNAs, miRNAs, mRNAs, and TFs in ESCC
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