Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, China.
Department of Pathophysiology, Third Military Medical University, Chongqing, China.
Cancer Med. 2019 Apr;8(4):1423-1433. doi: 10.1002/cam4.2010. Epub 2019 Feb 4.
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.
环状 RNA（circRNAs）是一大类非编码 RNA，它们在疾病发病机制和进展中具有潜在的调节作用。最近，circRNAs 已被发现在肝癌（HCC）组织中表达，并参与 HCC 的发生和转移。然而，circRNAs 在 HCC 患者外周血单核细胞（PBMCs）中的意义尚不清楚。在这项研究中，我们进行了 RNA 测序分析，以鉴定来自 4 名 HCC 患者和 3 名健康对照者的 PBMCs 中的 circRNAs，以确定 circRNAs 在 HCC 发病机制中的表达模式和 circRNAs 的分子调控网络。与健康对照者相比，我们发现 HCC 患者的 PBMCs 中有 58 个 circRNAs 表达显著改变（≥2 倍或≤0.5 倍）。进一步通过实时 RT-PCR 在 72 例 HCC 患者和 30 例对照者的 PBMCs 中验证了 6 个随机代表性 circRNAs（3 个上调和 3 个下调）。卡方检验表明，上调的 circRNA 候选物之一 circ_0000798 与临床变量相关。高表达的 circ_0000798 与 HCC 患者的总生存不良相关。受试者工作特征曲线分析进一步表明，circ_0000798 可区分 HCC 患者与健康对照者。最后，circ_0000798 的预测竞争性内源性 RNA 网络表明，它可能作为靶 microRNA 的“海绵”，随后调节 PBMCs 中靶基因的表达。总之，这是首次全面鉴定 HCC 患者 PBMCs 中失调的 circRNAs 的研究，其结果表明 PBMCs 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。
