Liu Hongli, Li Qi, Qi Han, Du Fengzhi, Qiu Yanli
Department of Stomatology, Cangzhou Medical College, Cangzhou, Hebei 061001, P.R. China.
Oncol Lett. 2022 Jun 20;24(2):270. doi: 10.3892/ol.2022.13390. eCollection 2022 Aug.
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.
本研究旨在通过微阵列分析鉴定差异表达的环状RNA(circRNA),并进一步探讨10种候选差异表达circRNA在舌鳞状细胞癌(TSCC)患者中的临床意义。共纳入60例行手术的TSCC患者,取5对TSCC组织及其癌旁对照(Ctrl)组织进行circRNA微阵列分析。随后,通过逆转录定量PCR(RT-qPCR)分析在60对肿瘤组织和对照组织中检测上调和下调最显著的5种差异表达circRNA,并进一步分析它们与肿瘤特征和总生存期(OS)的关系。通过主成分分析和热图分析,利用circRNA表达来区分TSCC组织和对照组织。与对照组织相比,TSCC组织中鉴定出134种上调的差异表达circRNA和67种下调的差异表达circRNA。这些差异表达circRNA在致癌信号通路中富集,包括“Wnt信号通路”和“MAPK信号通路”。在调控网络分析中,大多数差异表达circRNA表现出多个靶向微小RNA(miRNA)。这些发现通过RT-qPCR分析得到验证,结果表明,与对照组织相比,10种选定的候选差异表达circRNA(circ_0020048、circ_0000919、circ_0004525、circ_0002113、circ_0004029、circ_0004503、circ_0008752、circ_0002300和circ_0001811)中有9种在TSCC组织中的表达失调。5种差异表达circRNA(circ_0004503、circ_0008752、circ_0002300、circ_0020048和circ_0000919)的表达水平与病理分级或肿瘤临床分期相关。值得注意的是,只有一种差异表达circRNA(circ_0000919)的表达水平与总生存期降低相关。总之,本研究表明TSCC中存在异常的circRNA表达和潜在的circRNA-miRNA相互作用,并确定circ_0000919为TSCC管理的诊断和预后生物标志物。