Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of tongue

TLDR

Long non‑coding RNAs act as competing endogenous RNAs that bind microRNAs and regulate mRNA expression, a mechanism implicated in cancer initiation and progression, yet its role in squamous cell carcinoma of the tongue remains unclear; expression profiles from 138 TCGA patients were analyzed. The study aims to delineate the lncRNA‑miRNA‑mRNA ceRNA network in SCCT and propose a novel ceRNA that may aid diagnosis and treatment. Using TCGA data, differential expression of miRNAs, mRNAs, and lncRNAs was identified with limma, followed by GO/KEGG enrichment via clusterProfiler, survival analysis with the survival package, and network construction with GDCRNATools, yielding 1943 SCCT‑specific mRNAs, 107 lncRNAs, and 100 miRNAs. Ten mRNAs, nine lncRNAs, and eight miRNAs were significantly linked to overall survival, and one DE lncRNA, five DEmiRNAs, and three DEmRNAs were identified as key players in SCCT pathogenesis.

Abstract

Numerous studies have highlighted that long non-coding RNAs (lncRNAs) can bind to microRNA (miRNA) sites as competing endogenous RNAs (ceRNAs), thereby affecting and regulating the expression of mRNAs and target genes. These lncRNA-associated ceRNAs have been theorized to play a significant role in cancer initiation and progression. However, the roles and functions of the lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of the tongue (SCCT) are still unclear.The miRNA, mRNA and lncRNA expression profiles from 138 patients with SCCT were downloaded from The Cancer Genome Atlas database. We identified the differential expression of miRNAs, mRNAs, and lncRNAs using the limma package of R software. We used the clusterProfiler package for GO and KEGG pathway annotations. The survival package was used to estimate survival analysis according to the Kaplan-Meier curve. Finally, the GDCRNATools package was used to construct the lncRNA-miRNA-mRNA ceRNA network.In total, 1943 SCCT-specific mRNAs, 107 lncRNAs and 100 miRNAs were explored. Ten mRNAs (CSRP2, CKS2, ADGRG6, MB21D1, GMNN, RIPOR3, RAD51, PCLAF, ORC1, NAGS), 9 lncRNAs (LINC02560, HOXC13 - AS, FOXD2 - AS1, AC105277.1, AC099850.3, STARD4 - AS1, SLC16A1 - AS1, MIR503HG, MIR100HG) and 8 miRNAs (miR - 654, miR - 503, miR - 450a, miR - 379, miR - 369, miR - 190a, miR - 101, and let-7c) were found to be significantly associated with overall survival (log-rank p < 0.05). Based on the analysis of the lncRNA-miRNA-mRNA ceRNA network, one differentially expressed (DE) lncRNA, five DEmiRNAs, and three DEmRNAs were demonstrated to be related to the pathogenesis of SCCT.In this study, we described the gene regulation by the lncRNA-miRNA-mRNA ceRNA network in the progression of SCCT. We propose a new lncRNA-associated ceRNA that could help in the diagnosis and treatment of SCCT.