Diagnostic model of combined ceRNA and DNA methylation related genes in esophageal carcinoma

Abstract

Esophageal cancer is a common malignant tumor in the world, and the aim of this study was to screen key genes related to the development of esophageal cancer using a variety of bioinformatics analysis tools and analyze their biological functions. The data of esophageal squamous cell carcinoma from the Gene Expression Omnibus (GEO) were selected as the research object, processed and analyzed to screen differentially expressed microRNAs (miRNAs) and differential methylation genes. The competing endogenous RNAs (ceRNAs) interaction network of differentially expressed genes was constructed by bioinformatics tools DAVID, String, and Cytoscape. Biofunctional enrichment analysis was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The expression of the screened genes and the survival of the patients were verified. By analyzing GSE59973 and GSE114110, we found three down-regulated and nine up-regulated miRNAs. The gene expression matrix of GSE120356 was calculated by Pearson correlation coefficient, and the 11696 pairs of ceRNA relation were determined. In the ceRNA network, 643 lncRNAs and 147 mRNAs showed methylation difference. Functional enrichment analysis showed that these differentially expressed genes were mainly concentrated in the FoxO signaling pathway and were involved in the corresponding cascade of calcineurin. By analyzing the clinical data in The Cancer Genome Atlas (TCGA) database, it was found that four lncRNAs had an important impact on the survival and prognosis of esophageal carcinoma patients. QRT-PCR was also conducted to identify the expression of the key lncRNAs (RNF217-AS1, HCP5, ZFPM2-AS1 and HCG22) in ESCC samples. The selected key genes can provide theoretical guidance for further research on the molecular mechanism of esophageal carcinoma and the screening of molecular markers.

Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p/PAK6 axis

“…We focused on studying lncRNAs which were found upregulated in ESCC in the current study. LncRNAs, such as LUCAT1, KCNMB2-AS1, CASC15, MIAT, PTOV1-AS2, LINC00680, and RNF217-AS1 [ 45 – 50 ] were reported to be up-regulated in ESCC and other malignant tumors, validating our RNA-sequencing results. In particular, the high expression of four lncRNAs including LINC00680, AC092910.3, MIR4435-2HG, and GSEC were found to be correlated with poor prognosis in ESCC patients in lnCAR database [ 51 ], suggesting they are functionally important and clinically relevant (Fig.…”

Long non-coding RNA BBOX1-antisense RNA 1 enhances cell proliferation and migration and suppresses apoptosis in oral squamous cell carcinoma via the miR-3940-3p/laminin subunit gamma 2 axis

“…LncRNA gamma-butyrobetaine hydroxylase 1 (BBOX1)-antisense RNA 1 (AS1) exists as an oncogene in most tumor cells. Abnormally high expression levels of BBOX1-AS1 are observed in most cancers, such as lung [ 7 ], cervical [ 8 ], and esophageal cancers [ 9 ], and BBOX1-AS1 is strongly linked to the overall survival of patients with these cancers, which suggests that targeting BBOX1-AS1 may be used as a therapeutic approach for cancer treatment. However, the regulatory effects of BBOX1-AS1 on OSCC development have not yet been elucidated.…”

The short peptide encoded by long non-coding RNA RNF217-AS1 inhibits stomach cancer tumorigenesis, macrophage recruitment, and pro-inflammatory responses

“…Among these 8 lncRNAs, we further screened out 3 lncRNAs (LINC01503, NR2F1-AS1, and RNF217-AS1) for further investigations because the fold-changes of these 3 lncRNAs were the highest in TCGA SC samples versus the normal group. LINC01503 (Ding et al 2021 ), NR2F1-AS1 (Zuo et al 2021 ), and RNF217-AS1 (Guan et al 2020 ) have been found to be implicated in the pathogenesis of multiple cancers including SC. For instance, NR2F1-AS1 loss notably weakened the proliferative, migratory, and invasive abilities of SC cells (Li et al 2022a , b ).…”

“…RNF217-AS1, an antisense transcript for RNF217, is initially deemed to be a lncRNA transcript (Fontanari Krause et al 2014 ). RNF217-AS1 has been found to be differentially expressed and to be associated with the prognosis of patients in esophageal squamous cell cancer (ESCC) (Guan et al 2020 ). In this study, bioinformatics, ribosome-sequencing (Ribo-seq) dataset, and mass spectrometry (MS) dataset suggested that lncRNA RNF217-AS1 had peptide-coding potential, which was also validated by western blot assay.…”