Identification of circular RNA_0000919 as a potential diagnostic and prognostic biomarker of tongue squamous cell carcinoma using circular RNA microarray and reverse transcription-quantitative PCR analyses.

Abstract

The present study aimed to identify differentially expressed (DE) circular RNAs (circRNAs/circs) using microarray analysis and to further explore the clinical significance of 10 candidate DEcircRNAs in patients with tongue squamous cell carcinoma (TSCC). A total of 60 patients with TSCC who underwent surgery were enrolled and five pairs of TSCC and adjacent (Ctrl) tissues were used for circRNA microarray analysis. Subsequently, the top five upregulated and downregulated DEcircRNAs were detected by reverse transcription-quantitative PCR (RT-qPCR) analysis in 60 pairs of tumor and Ctrl tissues, and their association with tumor features and overall survival (OS) was further analyzed. circRNA expression was used to differentiate TSCC from Ctrl tissues by principal component and heatmap analyses. A total of 134 upregulated and 67 downregulated DEcircRNAs were identified in TSCC tissues compared with Ctrl tissues. The DEcircRNAs were enriched in oncogenic signaling, including the ‘Wnt signaling pathway’ and the ‘MAPK signaling pathway’. The majority of DEcircRNAs exhibited several target microRNAs (miRNAs) in regulatory network analysis. These findings were validated by RT-qPCR analysis and the results demonstrated that the expression levels of 9/10 selected candidate DEcircRNAs (circ_0020048, circ_0000919, circ_0004525, circ_0002113, circ_0004029, circ_0004503, circ_0008752, circ_0002300 and circ_0001811) were dysregulated in TSCC tissues compared with Ctrl tissues. The expression levels of five DEcircRNAs (circ_0004503, circ_0008752, circ_0002300, circ_0020048 and circ_0000919) were associated with pathological grade or tumor clinical stage. Notably, only the expression levels of one DEcircRNA (circ_0000919) were associated with decreased OS. In conclusion, the present study indicated aberrant circRNA expression and potential circRNA-miRNA interactions in TSCC and identified circ_0000919 as a diagnostic and prognostic biomarker for TSCC management.