Circular RNA expression profiles of peripheral blood mononuclear cells in hepatocellular carcinoma patients by sequence analysis
Circular RNA expression profiles of peripheral blood mononuclear cells in hepatocellular carcinoma patients by sequence analysis
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序列分析肝细胞癌患者外周血单个核细胞环状RNA表达谱
DOI：
10.1002/cam4.2010
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发表时间：
2019-04-01
期刊：
影响因子：
4
通讯作者：
Fan, Weiping
中科院分区：
文献类型：
--
作者：
Lei, Bo;Zhou, Jian;Fan, Weiping
环状RNA（CircRNA）是一类在疾病发病机制和进展中具有潜在调控作用的非编码RNA。近年来，研究发现circRNA在肝细胞癌（HCC）组织中表达，并参与HCC的发生、发展和转移。然而，肝癌患者外周血单核细胞（PBMC）中circRNA的意义仍不清楚。在这项研究中，进行RNA测序分析以鉴定来自4名HCC患者和3名健康对照的circRNA，以确定circRNA在PBMC中的表达模式以及circRNA在HCC发病机制中的分子调控网络。与健康病例相比，HCC患者PBMC中共有58种circRNA发生显著变化（≥2或≤0.5倍）。通过真实的时间RT-PCR在来自HCC患者和30名对照受试者的72个PBMC样品中进一步验证了6个随机代表性circRNA（3个上调和3个下调）。卡方检验表明，其中一个上调的circRNA候选者-circ_0000798-与临床变量相关。circ_0000798的高表达与HCC患者的总体生存率相关。受试者工作特征曲线分析进一步显示，circ_0000798可区分HCC患者和健康对照。最后，预测的竞争性内源性RNA网络circ_0000798表明，它可能充当靶microRNA的“海绵”，随后调节PBMC中靶基因的表达。总之，这是第一项全面鉴定HCC患者PBMC中失调的circRNA的研究，其发现表明PBMC中失调的circ_0000798具有作为诊断或预测HCC的方便生物标志物的潜力。
Circular RNAs (circRNAs) are a large class of noncoding RNAs that have potential regulatory roles in disease pathogenesis and progression. Recently, circRNAs have been found to be expressed in hepatocellular carcinoma (HCC) tissues and involved in the development and metastasis of HCC. However, the significance of circRNAs in peripheral blood mononuclear cells (PBMCs) of HCC patients remains unclear. In this study, RNA sequencing analysis was performed to identify circRNAs from four HCC patients and three healthy controls to determine the expression pattern of circRNAs in the PBMCs and the circRNAs’ molecular regulatory networks in HCC pathogenesis. A total of 58 circRNAs were found to be significantly changed (≥2 or ≤0.5‐fold) in the PBMCs of HCC patients compared with those of the healthy cases. Six random representative circRNAs (three up‐ and three down‐regulated) were further validated by real‐time RT‐PCR in 72 samples of PBMCs from HCC patients and 30 control subjects. Chi‐square test indicated that one of the up‐regulated circRNA candidates—circ_0000798—was correlated with clinical variables. Highly expressed circ_0000798 was associated with poor overall survival of HCC patients. Receiver operating characteristic curve analysis further revealed that circ_0000798 was discriminating HCC patients from healthy controls. Finally, the predicted competing endogenous RNA network of circ_0000798 showed that it might act as a “sponge” of target microRNAs, that would subsequently regulate the expression of target genes in PBMCs. In summary, this is the first study to comprehensively identify dysregulated circRNAs in PBMCs of HCC patients, and its findings suggest that dysregulated circ_0000798 in PBMCs has potential as a convenient biomarker for diagnosing or prognosticating HCC.