Cao Yuan, Shi Huirong, Ren Fang, Jia Yanyan, Zhang Ruitao
Department of Gynaecology, the First Affiliated Hospital of Zhengzhou University, China.
Department of Gynaecology, the First Affiliated Hospital of Zhengzhou University, China.
Exp Cell Res. 2017 Oct 1;359(1):185-194. doi: 10.1016/j.yexcr.2017.07.030. Epub 2017 Jul 25.
In this study, we reported that long non-coding RNA (lncRNA) CCAT1 was upregulated in epithelial ovarian cancer (EOC) tissues, and was associated with FIGO stage, histological grade, lymph node metastasis and poor survival of EOC patients. Multivariate Cox regression analysis showed that CCAT1 was an independent prognostic indicator. While CCAT1 downregulation inhibited EOC cell epithelial-mesenchymal transition (EMT), migration and invasion, CCAT1 upregulation promoted EOC cell EMT, migration and invasion. We further identified and confirmed that miR-152 and miR-130b were the targets of CCAT1, and CCAT1 functioned by targeting miR-152 and miR-130b. Subsequently, ADAM17 and WNT1, and STAT3 and ZEB1 were confirmed to be the targets of miR-152 and miR-130b, respectively, and could be regulated by CCAT1 in EOC cells. Knockdown of anyone of these four proteins inhibited EOC cell EMT, migration and invasion. Taken together, our study first revealed a critical role of CCAT1-miR-152/miR-130b-ADAM17/WNT1/STAT3/ZEB1 regulatory network in EOC cell metastasis. These findings provide great insights into EOC initiation and progression, and novel potential therapeutic targets and biomarkers for diagnosis and prognosis for EOC.
在本研究中，我们报道了长链非编码RNA（lncRNA）CCAT1在上皮性卵巢癌（EOC）组织中上调，且与EOC患者的国际妇产科联盟（FIGO）分期、组织学分级、淋巴结转移及不良生存相关。多因素Cox回归分析表明，CCAT1是一个独立的预后指标。CCAT1下调可抑制EOC细胞上皮-间质转化（EMT）、迁移和侵袭，而CCAT1上调则促进EOC细胞EMT、迁移和侵袭。我们进一步鉴定并证实miR-152和miR-130b是CCAT1的靶标，且CCAT1通过靶向miR-152和miR-130b发挥作用。随后，分别证实ADAM17和WNT1以及STAT3和ZEB1是miR-152和miR-130b的靶标，且在EOC细胞中可受CCAT1调控。敲低这四种蛋白中的任何一种均可抑制EOC细胞EMT、迁移和侵袭。综上所述，我们的研究首次揭示了CCAT1-miR-152/miR-130b-ADAM17/WNT1/STAT3/ZEB1调控网络在EOC细胞转移中的关键作用。这些发现为EOC的发生和发展提供了深刻见解，并为EOC的诊断和预后提供了新的潜在治疗靶点和生物标志物。
