Han Zhiyi, Feng Wenxing, Hu Rui, Ge Qinyu, Sun Xinfeng, Ma Wenfeng, Zhang Wei, Xu Shaomin, Zhan Bolin, Zhang Lai, Li Qun, Zhou Xiaozhou
Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong 518033, P.R. China.
Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China.
Exp Ther Med. 2021 Dec;22(6):1467. doi: 10.3892/etm.2021.10902. Epub 2021 Oct 20.
Circular RNAs (circRNAs) are differentially expressed in various cancer types. The present study aimed to investigate the expression and clinical implication of circRNAs in hepatocellular carcinoma (HCC) and to evaluate the potential of circRNAs as diagnostic biomarkers for HCC. CircRNA expression was profiled in 19 patients with HCC and 19 normal controls using ribosomal RNA-depleted RNAs. Differentially expressed circRNAs (DE-circRNAs) between HCC and controls were identified using CIRI2 and distinct circRNA expression signatures were screened. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to predict the potential functions of these DE-circRNAs and the circRNA-miRNA-mRNA regulatory networks were then constructed. Several DE-circRNAs were selected and confirmed by RT-qPCR. A total of 40 DE-circRNAs (27 upregulated and 13 downregulated) were identified between patients with HCC and controls. Functional annotation indicated that these DE-circRNAs were involved in cellular components, molecular functions and cancer-associated pathways related to HCC. These included pathways in cancer, TNF signaling pathway, hepatitis B, hepatitis C and hepatocyte differentiation. The circRNA-miRNA-mRNA regulatory network was generated based on 11 candidate circRNAs. Receiver operating characteristic curve analysis indicated that (hsa)_circ_0073239, hsa_circ_007090, hsa_circ_0008304, hsa_circ_0017586, hsa_circ_0000369 and hsa_circ_0001181 may serve as potential biomarkers for HCC. Results from Cell Counting Kit-8 assay suggested that small interfering RNA targeting hsa_circ_0001181 reduced the proliferation of HepG2 cells, which implicated it as a potential therapeutic target for HCC. Therefore, in the present study, the differential expression pattern and important role of circRNAs in HCC were determined. The present results highlight the diagnostic potential of circRNAs in HCC and provide novel insight into the development of and treatment approaches for HCC.
环状RNA（circRNAs）在多种癌症类型中存在差异表达。本研究旨在探讨circRNAs在肝细胞癌（HCC）中的表达及临床意义，并评估circRNAs作为HCC诊断生物标志物的潜力。使用核糖体RNA去除的RNA对19例HCC患者和19例正常对照进行circRNA表达谱分析。利用CIRI2鉴定HCC与对照之间差异表达的circRNAs（DE-circRNAs），并筛选出不同的circRNA表达特征。采用基因本体论和京都基因与基因组百科全书预测这些DE-circRNAs的潜在功能，随后构建circRNA- miRNA- mRNA调控网络。选择了几个DE-circRNAs并通过RT-qPCR进行验证。在HCC患者与对照之间共鉴定出40个DE-circRNAs（27个上调和13个下调）。功能注释表明，这些DE-circRNAs参与了与HCC相关的细胞成分、分子功能和癌症相关途径。这些途径包括癌症、TNF信号通路、乙型肝炎、丙型肝炎和肝细胞分化。基于11个候选circRNAs构建了circRNA- miRNA- mRNA调控网络。受试者工作特征曲线分析表明，（hsa）_circ_0073239、hsa_circ_007090、hsa_circ_0008304、hsa_circ_0017586、hsa_circ_0000369和hsa_circ_0001181可能作为HCC的潜在生物标志物。细胞计数试剂盒8检测结果表明，靶向hsa_circ_0001181的小干扰RNA降低了HepG2细胞的增殖，这表明它是HCC的潜在治疗靶点。因此，在本研究中，确定了circRNAs在HCC中的差异表达模式和重要作用。本研究结果突出了circRNAs在HCC中的诊断潜力，并为HCC的发生发展和治疗方法提供了新的见解。
