Analysis of Differentially Expressed Long Non-coding RNAs and the Associated TF-mRNA Network in Tongue Squamous Cell Carcinoma

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.

Evolutionary route of nasopharyngeal carcinoma metastasis and its clinical significance

“…In addition, single-cell RNA sequencing (scRNA-seq), a high-resolution technology, could provide new insights into tumour evolution and has been successfully used to reconstruct clonal evolutionary trajectories during chemotherapy in breast cancer 12 . scRNA-seq could also be used to dissect the intratumour heterogeneity (ITH) of primary and metastatic tumour ecosystems in NPC 13 and draw a map of the immune phenotype in NPC [14][15][16][17][18][19][20][21][22] . Studies that focuses on the evolutionary route of metastasis in NPC are still lacking.…”

lncKRT16P6 promotes tongue squamous cell carcinoma progression by sponging miR‑3180 and regulating GATAD2A expression

“…Previously, we screened for differentially expressed lncRNAs by analyzing six pairs of TSCC and healthy adjacent normal tissues through high-throughput RNA sequencing (Kangchen BioTech Co., Ltd.) ( 24 ) and identified the significantly overexpressed lncRNA lncKRT16P6. RT-qPCR was applied to detect the expression of differentially expressed lncRNAs.…”

“…Thus, further insight into lncRNA-dependent gene-regulatory mechanisms will provide predictive biomarkers and individual treatments for TSCC. The present study, based on our previous research results (24), performed an in-depth analysis of lncRNA expression profiles and identified a novel lncRNA, keratin 16 pseudogene 6 (lncKRT16P6), which was upregulated in TSCC tissues and cell lines and associated with TSCC tumor stage and differentiation grade. The aim of the present study was to explore the specific regulatory mechanism by which lncKRT16P6 promoted the occurrence and development of TSCC.…”

Long Intergenic Non-Coding RNAs in HNSCC: From “Junk DNA” to Important Prognostic Factor

“…Long intergenic non-protein-coding RNA 511 (LINC00511) is up-regulated in different malignancies including also HNSCC [99]. This molecule has a variety of functions, including regulation of the developmental process, apoptosis, programmed cell death, focal adhesion through hemostasis, and different carcinogenic pathways [100].…”