Downregulation of ZC3H14 driven by chromosome 14q31 deletion promotes hepatocellular carcinoma progression by activating integrin signaling
Downregulation of ZC3H14 driven by chromosome 14q31 deletion promotes hepatocellular carcinoma progression by activating integrin signaling
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染色体 14q31 缺失驱动的 ZC3H14 下调通过激活整合素信号传导促进肝细胞癌进展。
DOI：
10.1093/carcin/bgy146
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发表时间：
2019
期刊：
影响因子：
4.7
通讯作者：
Zhou Gangqiao
中科院分区：
文献类型：
--
作者：
Zhang Chuxiao;Cao Pengbo;Yang Aiqing;Xia Xia;Li Yuanfeng;Shi Mengting;Yang Ying;Wei Xiaojun;Yang Chun;Zhou Gangqiao
肝细胞癌（HCC）是全球癌症相关死亡的第三大原因。在HCC中经常观察到染色体14q31.1-32.13处的基因组拷贝数缺失;然而，该位点的相关功能靶标尚未得到很好的确定。在这里，我们进行了整合基因组分析，并确定锌指CCCH型含有14（ZC 3 H14）作为一个有希望的候选人在14q31.1-32.13。我们观察到原发性肝癌组织中频繁的拷贝数缺失（17.1%）和ZC 3 H14下调。ZC 3 H14的下调与HCC患者的不良预后显著相关。ZC 3 H14在肝癌细胞系中的过表达显著抑制肝癌细胞的体外生长和体内转移。相反，ZC 3 H14的RNA干扰沉默抑制了其抑瘤功能。在机制上，结合生物信息学分析和实验研究，我们证明ZC 3 H14的缺失通过增强整合素途径促进HCC的进展。这项研究表明，ZC 3 H14作为一种新的肿瘤抑制因子，是一个候选的肝癌患者的预后生物标志物。
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Genomic copy number deletion at chromosome 14q31.1–32.13 was frequently observed in HCC; however, the relevant functional target(s) at that locus is not well determined. Here, we performed integrative genomic analyses and identifiedzinc finger CCCH-type containing 14 (ZC3H14)as a promising candidate at 14q31.1–32.13. We observed frequent copy number deletion (17.1%) and downregulation ofZC3H14in primary HCC tissues. Downregulation ofZC3H14was significantly associated with poor outcomes of patients with HCC. Overexpression of ZC3H14 in HCC cell lines significantly suppressed HCC cells growthin vitroand metastasisin vivo. In contrast, RNA interference silencing ofZC3H14inhibited its tumor-suppressive function. Mechanismly, through combing bioinformatics analyses and experimental investigation, we demonstrated that loss ofZC3H14promotes HCC progression through enhancing integrin pathway. This study suggests that ZC3H14 functions as a novel tumor suppressor and is a candidate prognostic biomarker for HCC patients.