Network-Based Method to Investigate the Promoted Cell Apoptosis Mechanisms of Oridonin in OSCC through the RNA-Transcriptome.

The morbidity of oral cancer is high in the world. Oridonin is a traditional Chinese medicine that can effectively inhibit oral squamous cell carcinoma (OSCC) growth, but its mechanism remains unclear. Our previous data showed that oridonin inhibited CAL-27 cell proliferation and promoted apoptosis. Herein, we explored the mechanism and target of oridonin in human OSCC through RNA sequencing and integration of multiple bioinformatics analysis strategies. Differences in gene expression can be analyzed with RNA sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), gene set enrichment analysis (GSEA), Disease Ontology (DO), and other enrichment analyses were used to evaluate differentially expressed genes (DEGs). Protein-protein interaction (PPI) networks were built via the STRING database. It was found that tumor necrosis factor (TNF) signaling pathway, cytokine-cytokine receptor interaction, and nuclear factor-kappa B (NF-kappaB) signaling pathway were associated with the therapeutic effects of oridonin in OSCC. Three key genes (BIRC3, TNFSF10, and BCL6) were found to associate with cell apoptosis in OSCC cells treated with oridonin. Quantitative PCR assays verified the expression of apoptosis-related DEGs: TNFSF10, BIRC3, AIFM2, BCL6, BCL2L2, and Bax. Western blots were employed for verifying proteins expression associated with DEGs: cleaved caspase 3, Bax, Bcl-w, anti-cIAP2, and anti-TRAIL. In conclusion, our findings reveal the molecular pathways and targets by which oridonin can treat and induce cytotoxic effects in OSCC: by affecting the signaling including TNF, NF-κB, and cytokine-cytokine receptor interaction and by regulating the key gene BIRC3, TNFSF10, and BCL6. It should be noted that further clinical trial validation is very necessary. Combined with current research trends, our existing research may provide innovative research drugs for the treatment of OSCC.

Circular RNAs as a Diagnostic Biomarker in Oral Squamous Cell Carcinoma: A Meta-Analysis.

PURPOSE: Studies have found a positive correlation between various cancers and circular RNAs (circRNAs), which are newly discovered noncoding RNAs. However, limited scientific evidence is available to prove the clinical value of circRNAs in the presentation of oral squamous cell carcinoma (OSCC). This study aimed to explore comprehensively the potential of circRNAs as diagnostic indexes of OSCC. METHODS: Online databases were systematically searched to identify published literature on the discovery of circRNAs in OSCC. Data were acquired from each reviewed study and collated to create a 2 × 2 eventuality table. Hierarchical analysis of the literature was conducted for the type of cancer, year of publication, and the sample size of each study. The diagnostic accuracy was calculated using indexes such as the pooled sensitivity and specificity, and assessed critically using the Quality Assessment for Studies of Diagnostic Accuracy 2. RESULTS: This meta-analysis included findings of 6 studies on 335 patients diagnosed with OSCC. These 6 studies examined 7 circRNAs, 5 in tissues and 2 in the saliva of patients with OSCC. When used as a diagnostic tool for OSCC, circRNAs manifested a sensitivity level of 0.72 (95% confidence interval: 0.67 to 0.76) and a degree of specificity of 0.81 (95% confidence interval: 0.76 to 0.85), with a general projected probability rate of 3.82 (95% confidence interval: 2.98 to 4.91) being positive and 0.35 (95% confidence interval: 0.29 to 0.41) being negative. The combined probability rate was 11.07 (95% confidence interval: 7.64 to 16.04), comprising a total of 0.76 (95% confidence interval: 0.72 to 0.79) of the region under the curve. A higher diagnostic value was found for salivary circRNAs (diagnostic odds ratio = 17.52; 95% CI: 10.11 to 30.35) than for tissue circRNAs (diagnostic odds ratio = 8.47; 95% CI: 5.6 to 12.83). This indicated that circRNAs showed a good discrimination ability as biomarkers of OSCC. CONCLUSIONS: circRNAs showed high accuracy in the diagnosis of OSCC and could be used as prospective biomarkers to facilitate the diagnostic process.