筛选差异环状RNA表达谱揭示hsa_circ_0004018与肝细胞癌相关。

Screening differential circular RNA expression profiles reveals hsa_circ_0004018 is associated with hepatocellular carcinoma.

作者信息

Fu Liyun, Yao Ting, Chen Qingqing, Mo Xiaoyan, Hu Yaoren, Guo Junming

机构信息

Department of Hepatology, Ningbo No. 2 Hospital and The Affiliated Hospital, Medical School of Ningbo University, Ningbo 315010, China.

Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo 315211, China.

出版信息

Oncotarget. 2017 Apr 6;8(35):58405-58416. doi: 10.18632/oncotarget.16881. eCollection 2017 Aug 29.

Abstract

Circular RNAs (circRNAs) have been emerged as an indispensable part of endogenous RNA network. However, the expression significance of circRNAs in hepatocellular carcinoma (HCC) is rarely revealed. The aim of this study was to determine the circRNA expression profile in HCC, and to investigate their clinical significances and relevant mechanisms for cancer progression. The global circRNA expression profile in HCC was measured by circRNA microarray. Levels of one representative circRNAs, hsa_circ_0004018, were confirmed by real-time reverse transcription-polymerase chain reaction. The expression levels of hsa_circ_0004018 in HCC were significantly lower compared with para-tumorous tissue (<0.001). Our data further showed that lower expression of hsa_circ_0004018 was correlated with serum alpha-fetoprotein (AFP) level, tumor diameters, differentiation, Barcelona Clinic Liver Cancer stage and Tumor-node-metastasis stage. More importantly, we detected liver tissues from chronic hepatitis, cirrhosis and HCC patients; and found that hsa_circ_0004018 harbored HCC-stage-specific expression features in diverse chronic liver diseases (<0.001). The area under receiver operating characteristic curve was up to 0.848 (95% CI=0.803-0.894, <0.001). The sensitivity and specificity were 0.716 and 0.815, respectively. Finally, hsa_circ_0004018 might be involved in cancer-related pathways via interactions with miRNAs.

摘要

环状RNA(circRNAs)已成为内源性RNA网络中不可或缺的一部分。然而,circRNAs在肝细胞癌(HCC)中的表达意义鲜有揭示。本研究旨在确定HCC中circRNA的表达谱,并探讨其临床意义及癌症进展的相关机制。通过circRNA微阵列检测HCC中的整体circRNA表达谱。通过实时逆转录-聚合酶链反应确认一种代表性circRNA hsa_circ_0004018的水平。与癌旁组织相比,HCC中hsa_circ_0004018的表达水平显著降低(<0.001)。我们的数据进一步表明,hsa_circ_0004018的低表达与血清甲胎蛋白(AFP)水平、肿瘤直径、分化程度、巴塞罗那临床肝癌分期及肿瘤-淋巴结-转移分期相关。更重要的是,我们检测了慢性肝炎、肝硬化和HCC患者的肝组织;发现hsa_circ_0004018在不同慢性肝病中具有HCC分期特异性表达特征(<0.001)。受试者工作特征曲线下面积高达0.848(95%CI = 0.803 - 0.894,<0.001)。敏感性和特异性分别为0.716和0.815。最后,hsa_circ_0004018可能通过与miRNA相互作用参与癌症相关通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c53/5601662/5381d5d2dc53/oncotarget-08-58405-g001.jpg

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