ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways.
ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways.
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ZKSCAN1基因及其相关环状RNA（circZKSCAN1）均通过不同的信号通路抑制肝细胞癌细胞的生长、迁移和侵袭
DOI：
10.1002/1878-0261.12045
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发表时间：
2017-04
影响因子：
6.6
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Yao Z;Luo J;Hu K;Lin J;Huang H;Wang Q;Zhang P;Xiong Z;He C;Huang Z;Liu B;Yang Y
越来越多的证据表明，环状RNA（circRNA）参与癌症的发展，但人类circRNA的调控和功能仍然在很大程度上未知。在这项研究中，我们证明，ZKSCAN 1，锌指家族基因，表达在两个线性和环状（circZKSCAN 1）形式的RNA在人肝细胞癌（HCC）组织和细胞系。在这里，我们分析了102例患者的队列，发现ZKSCAN 1 mRNA和circZKSCAN 1在HCC样本中的表达显著低于（P < 0.05）通过逆转录PCR（RT-PCR）匹配的相邻非肿瘤组织。ZKSCAN 1的低表达水平仅与肿瘤大小相关（P = 0.032），而cirZKSCAN 1的表达水平在不同肿瘤数目（P < 0.01）、肝硬化（P = 0.031）、血管浸润（P = 0.002）、显微镜下血管浸润（P = 0.002）以及肿瘤分级（P < 0.001）的患者中存在差异。沉默ZKSCAN 1 mRNA和circZKSCAN 1促进细胞增殖、迁移和侵袭。相反，这两种形式的RNA的过表达在体内和体外抑制HCC进展。两种形式的RNA的沉默或过表达不会相互干扰。RNA-seq揭示了观察到的效应的非常不同的分子基础; ZKSCAN 1 mRNA主要调节细胞代谢，而circZKSCAN 1介导了几种癌症相关的信号通路，这表明ZKSCAN 1 mRNA和circRNA的作用是非冗余的。总之，我们的研究结果揭示了两种翻译后产物（ZKSCAN 1 mRNA和circZKSCAN 1），它们相互密切合作，抑制HCC的生长，迁移和侵袭。cirZKSCAN 1可能是诊断HCC的一个有用指标。
There is increasing evidence that circular RNA (circRNA) are involved in cancer development, but the regulation and function of human circRNA remain largely unknown. In this study, we demonstrated that ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular (circZKSCAN1) forms of RNA in human hepatocellular carcinoma (HCC) tissues and cell lines. Here, we analyzed a cohort of 102 patients and found that expression of both ZKSCAN1mRNA and circZKSCAN1 was significantly lower (P < 0.05) in the HCC samples compared with that in matched adjacent nontumorous tissues by reverse transcription PCR (RT‐PCR). The low expression level of ZKSCAN1 was only associated with tumor size (P = 0.032), while the cirZKSCAN1 levels varied in patients with different tumor numbers (P < 0.01), cirrhosis (P = 0.031), vascular invasion (P = 0.002), or microscopic vascular invasion (P = 0.002), as well as with the tumor grade (P < 0.001). Silencing both ZKSCAN1mRNA and circZKSCAN1 promoted cell proliferation, migration, and invasion. In contrast, overexpression of both forms of RNA repressed HCC progression in vivo and in vitro. Silencing or overexpression of both forms of RNA did not interfere with each other. RNA‐seq revealed a very different molecular basis for the observed effects; ZKSCAN1mRNA mainly regulated cellular metabolism, while circZKSCAN1 mediated several cancer‐related signaling pathways, suggesting a nonredundant role for ZKSCAN1mRNA and circRNA. In conclusion, our results revealed two post‐translational products (ZKSCAN1mRNA and circZKSCAN1) that cooperated closely with one another to inhibit growth, migration, and invasion of HCC. cirZKSCAN1 might be a useful marker for the diagnosis of HCC.
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