Abstract
Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in tongue squamous cell carcinoma (TSCC) tumorigenesis. However, the comprehensive regulation of lncRNAs-transcription factors (TFs)-messenger RNAs (mRNAs) in TSCC remains largely unknown. The purpose of this study was to identify aberrantly expressed lncRNAs and the associated TF-mRNA network in TSCC. To explore lncRNA and mRNA expression profiles and their biological functions in TSCC, we surveyed the lncRNA and mRNA expression profiles of TSCC and adjacent tissues using next-generation RNA sequencing in six patients. Thousands of significantly differentially expressed lncRNAs (DELs) and mRNAs (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to demonstrate the principal functions of the significantly dysregulated lncRNAs and genes. A total of 40 DELs were screened between TSCC and adjacent non-cancerous tissues. Results obtained from GEPIA and StarBase confirmed the expression levels of nine pivotal DELs obtained in our study. Three of the nine deregulated DELs were identified to have a significant impact on the overall survival of TSCC patients, which were evaluated with GEPIA and StarBase. LncMAP was used to predict the lncRNA-TF-mRNA triplets in TSCC. Furthermore, based on these results, we established lncRNA-TF-mRNA coexpression networks for the up- and downregulated lncRNAs using Cytoscape. We also found that among the nine pivotal lncRNAs, there is limited research on the abnormally expressed lncRNAs, including RP11-54H7.4, CTD-2545M3.8, RP11-760H22.2, RP4-791M13.3, and LINC01405, in TSCC pathogenesis. This is the first study to show that RP11-54H7.4, LINC00152, and LINC01405 can be acted as a prognostic target for TSCC. Our findings provide a novel perspective and lay the foundation for future research on the potential roles of lncRNAs, TFs, and mRNAs in TSCC. Verification of the potential lncRNA-TF-mRNA regulatory networks will provide a more comprehensive understanding of the pathogenesis of TSCC.
Highlights
As the most lethal and commonly occurring oral malignancy, oral squamous cell carcinoma (OSCC) accounts for 95% of all oral cancer diagnoses and causes more than 500,000 deaths per year [1]
4,224 messenger RNAs (mRNAs) and 1,470 long non-coding RNAs (lncRNAs) were differentially expressed between tongue squamous cell carcinoma (TSCC) tumor and adjacent tissues
Our results showed that oxidative phosphorylation, RNA transport, and mRNA surveillance pathway were associated with the dysregulated lncRNAs
Summary
As the most lethal and commonly occurring oral malignancy, oral squamous cell carcinoma (OSCC) accounts for 95% of all oral cancer diagnoses and causes more than 500,000 deaths per year [1]. 25–40% of OSCCs are diagnosed as tongue squamous cell carcinoma (TSCC) [2]. TSCC is characterized by frequent lymphoid metastasis, a high rate of regional recurrence, and a poor prognosis. Upregulation of the lncRNA HOTTIP in TSCC patients indicates a poor clinical prognosis [7]. High expression of the lncRNA UCA1 has been linked to the migratory ability of epithelial cancer cells and regional lymph node metastasis in TSCC [11]. The lncRNAs KCNQ1OT1 and SNHG17 act as competing endogenous RNAs (ceRNAs) to regulate cell proliferation and cancer progression in TSCC [12, 13]
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