Cai Sina, Zhang Yuqin, Zhang Xiaona, Wang Liping, Wu Ziqing, Fang Weiyi, Chen Xiaohua
Department of Oncology, the Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
Department of Clinical Oncology, The Affiliated Chenzhou Hospital, Hengyang Medical School, University of South China, Chenzhou, China.
J Gastrointest Oncol. 2022 Apr;13(2):510-526. doi: 10.21037/jgo-22-137.
Recent studies indicate that non-coding circular RNAs (circRNAs) are involved in the development of esophageal carcinoma (EC). This study aimed to identify differential expression of circRNAs in EC, which can provide potential biomarkers and therapeutic targets for EC treatment and improve the understanding of tumorigenesis mechanism.
First, samples (n=5) of EC tissues and adjacent normal tissue were sent for circRNA microarray detection, Second, further bioinformatic analysis was performed, including circRNA-microRNA (miRNA), co-expression network analysis, Spearman correlation test, and cancer-related circRNA-miRNA axis analysis. Finally, the expression of circRNA that our analysis predicted to be hub genes was verified in samples (n=15) of EC tissues and adjacent normal tissue by real-time polymerase chain reaction (RT-PCR).
Microarray identified 102 upregulated and 67 significantly downregulated circRNAs were in EC patients' tumors relative to adjacent normal tissue. One upregulated circRNA () showed the most connection with MREs, therefore was regarded as the hub gene by the Spearman correlation test. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that four primary pathways (mRNA surveillance, cytoskeleton actin regulation, spliceosome, and the NOD-like receptor signaling pathway) were predicted in the hub circRNA's five connected miRNA response elements (MREs). Furthermore, cancer-related circRNA-miRNA axis analyses showed that and its four connected MREs participated in the cancer-related pathway. RT-PCR showed that and were significantly increased in the tumor tissues of EC patients.
Abnormal expression of circRNAs was involved in the tumorigenesis of EC. Key circRNAs, namely and , may be as potential biomarkers and therapeutic targets for the treatment of EC.
近期研究表明,非编码环状RNA(circRNAs)参与食管癌(EC)的发生发展。本研究旨在鉴定EC中circRNAs的差异表达,为EC治疗提供潜在的生物标志物和治疗靶点,并增进对肿瘤发生机制的理解。
首先,将5例EC组织样本和相邻正常组织样本送去进行circRNA微阵列检测。其次,进行进一步的生物信息学分析,包括circRNA-微小RNA(miRNA)、共表达网络分析、Spearman相关性检验以及癌症相关circRNA-miRNA轴分析。最后,通过实时聚合酶链反应(RT-PCR)在15例EC组织样本和相邻正常组织样本中验证我们分析预测为枢纽基因的circRNA的表达。
微阵列鉴定出相对于相邻正常组织,EC患者肿瘤中有102种上调和67种显著下调的circRNAs。一种上调的circRNA与微小RNA反应元件(MREs)的连接最多,因此通过Spearman相关性检验被视为枢纽基因。京都基因与基因组百科全书(KEGG)通路富集分析表明,在枢纽circRNA的五个连接的miRNA反应元件(MREs)中预测到四个主要通路(mRNA监测、细胞骨架肌动蛋白调节、剪接体和NOD样受体信号通路)。此外,癌症相关circRNA-miRNA轴分析表明,该circRNA及其四个连接的MREs参与了癌症相关通路。RT-PCR显示,该circRNA在EC患者的肿瘤组织中显著增加。
circRNAs的异常表达参与了EC的肿瘤发生。关键的circRNAs,即该circRNA和另一种circRNA,可能作为EC治疗的潜在生物标志物和治疗靶点。