RESUMEN
Background: Nasopharyngeal carcinoma (NPC) is particularly prevalent in East and Southeast Asia. Competing endogenous RNA (ceRNA) networks are known to play an essential role in the emergence of various diseases, including cancer. Building a network of protein-protein interactions (PPIs) and ceRNAs can facilitate the detection of potential connections between messenger RNAs (mRNAs) and various non-coding RNAs. However, the precise role of ceRNA networks in NPC has not been examined in detail. Therefore, the primary aim of the present study was to characterize a ceRNA network for NPC. Methods: Datasets of microRNA (miRNA), long non-coding RNA (lncRNA), and mRNA microarrays were downloaded from the Gene Expression Omnibus (GEO) database. Data were standardized and differentially expressed genes (DEGs) were screened using the limma package. The ClusterProfiler software suite was used to perform enrichment analysis of differentially expressed mRNAs using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) techniques. Results: A total of 160 lncRNAs, 8 miRNAs, and 147 mRNAs were differentially expressed in NPC samples. A ceRNA network was constructed using four lncRNAs, five miRNAs, and one mRNA that were dysregulated in NPC. Cellular functions of the abnormally expressed mRNAs were mainly associated with tumor cell movement, cell growth and proliferation, cell cycle, invasion, and metastasis. Conclusions: The ceRNA network constructed herein clarified the regulatory mechanisms through which lncRNAs act as ceRNAs and participate in NPC development. Notably, lncRNAs, miRNAs, and mRNAs identified in this ceRNA network can serve as therapeutic targets and prognostic biomarkers for NPC.
RESUMEN
Oral mucositis is the most common oral complication of cancer patients receiving radiotherapy or chemotherapy, leading to poor quality of life. Increasing clinical studies demonstrated that thalidomide (THD) can effectively ameliorate radiation-induced oral mucositis (RIOM). Here we established an experimental mouse model, radiation-induced human oral epithelial cells (HOECs), and further investigate the underlying mechanism the THD protective effect against RIOM. Combined with RNA sequencing result, we selected the gene nuclear factor of activated T cells c2 (NFATC2) as the most interesting candidate. THD downregulated NFATC2 expression, attenuated human oral epithelial cells (HOECs) apoptosis and promoted pro-inflammatory factors secretion. Further studies show that overexpression of NFATC2 in HOECs promotes cells apoptosis and pro-inflammatory cytokines level, while inhibition of NFATC2 present an opposite effect. Additionally, the regulatory miRNA of NFATC2 was predicted using StarBase, and the targeting relationship between miR-9-3p and NFATC2 was confirmed using a dual-luciferase reporter gene assay. miR-9-3p mimic reversed the elevated cell apoptosis and pro-inflammatory cytokines level by radiation or NFATC2-overexpression. Furthermore, NFATC2 upregulated the phosphorylation of p65, thus activating the NF-κB pathway in RIOM; while miR-9-3p reduced this effect. In conclusion, THD attenuates oral epithelial cell apoptosis and pro-inflammatory cytokines secretion induced by radiotherapy via the miR-9-3p/NFATC2/NF- NF-κB axis.
