Reconstruction and analysis of the aberrant lncRNA-miRNA-mRNA network based on competitive endogenous RNA in adenoid cystic carcinoma of the salivary gland.

Background: The aim of this work was to investigate the competing endogenous RNA (ceRNA) network in adenoid cystic carcinoma of the salivary gland (SACC).

Methods: Differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) between cancer tissues and normal salivary gland (NSG) in ACC were identified using data from the Gene Expression Omnibus (GEO) database. Functional annotation and pathway enrichment analysis of DEmRNAs were performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The miRNAs that are targeted by lncRNAs were predicted using miRanda and PITA, while the target mRNAs of miRNAs were retrieved from miRanda, miRWalk, and TargetScan. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and then we constructed the lncRNA-miRNA-mRNA networks of ACC.

Results: Differentially expressed RNAs were identified in SACC. Upon comparing cancer tissues and NSG tissues, 103 upregulated and 52 downregulated lncRNAs and 745 upregulated and 866 downregulated mRNAs were identified in GSE88804; in addition, 39 upregulated and 43 downregulated miRNAs were identified in GSE117275. GO enrichment analyses revealed that the most relevant GO terms were regulation of transcription DNA-templated, transcription DNA-templated, and cell division. KEGG pathway enrichment analysis showed that differentially expressed genes (DEGs) were mainly enriched in the cell cycle, pathways in cancer, PI3K-Akt signaling pathway, breast cancer, and microRNAs in cancer. The PPI network consisted of 27 upregulated and 54 downregulated mRNAs. By constructing ceRNA network, NONHSAT251752.1-hsa-miR-6817-5p-NOTCH1, NONHSAT251752.1-hsa-miR-204-5p/hsa-miR-138-5p-CDK6 regulatory axises were identified and all genes in the network were verified by qRT-PCR.

Conclusions: The present study constructed ceRNA networks in SACC and provided a novel perspective of the molecular mechanisms for SACC.