Purpose

Epithelial ovarian cancer (EOC) is a highly fatal gynecological cancer. A long noncoding RNA (lncRNA) gastric cancer-associated lncRNA1 (GClnc1) has been revealed to play critical roles in metastasis. Therefore, the present study aims to explore the correlation between GClnc1 and the metastasis and progression of EOC.

Methods

First, 57 paired EOC and paracancerous tissues were collected to detect GClnc1 expression by RT-qPCR. Subsequently, OVC1 and SKOV3 cells with GClnc1 silencing/overexpression were developed to detect changes in cell activity, apoptosis, migration and invasion abilities. Then, the subcellular localization of GClnc1 was detected by nuclear/cytoplasmic fractionation, ISH and FISH assays. The binding relationships between GClnc1 and forkhead box protein C2 (FOXC2), and between FOXC2 and NOTCH1 were predicted and verified.

Results

GClnc1 was significantly overexpressed in EOC tissues, and knockdown of GClnc1 inhibited cell viability and promoted apoptosis. Moreover, GClnc1 in the nucleus bound to the transcription factor FOXC2, thereby activating the transcription of NOTCH1. NOTCH1 overexpression enhanced the proliferation and epithelial-mesenchymal transition of SKOV3 and OVC1 cells. Moreover, NOTCH1 activated the NF-κB/Snail signaling. Finally, in vivo experiments demonstrated that GClnc1 knockdown suppressed the growth and metastasis of SKOV3 and OVC1 cells in vivo.

Conclusions

GClnc1 promoted NOTCH1 transcription by recruiting FOXC2, thereby activating the NF-κB/Snail signaling and promoting EOC cell growth and metastasis.

中文翻译：

---

长时间的非编码RNA GClnc1敲低可以通过募集FOXC2来破坏NOTCH1 /NF-κB/ Snail通路来抑制上皮性卵巢癌的进展

目的

上皮性卵巢癌（EOC）是高度致命的妇科癌症。长期的非编码RNA（lncRNA）胃癌相关的lncRNA1（GClnc1）已被发现在转移中起关键作用。因此，本研究旨在探讨GClnc1与EOC的转移和进展之间的相关性。

方法

首先，收集57对配对的EOC和癌旁组织，以通过RT-qPCR检测GClnc1表达。随后，开发了具有GClnc1沉默/过表达的OVC1和SKOV3细胞，以检测细胞活性，凋亡，迁移和侵袭能力的变化。然后，通过核/细胞质分级分离，ISH和FISH检测来检测GClnc1的亚细胞定位。预测并验证了GClnc1和叉头盒蛋白C2（FOXC2）之间，以及FOXC2和NOTCH1之间的结合关系。

结果

GClnc1在EOC组织中明显过表达，而敲低GClnc1则抑制细胞活力并促进细胞凋亡。此外，细胞核中的GClnc1与转录因子FOXC2结合，从而激活NOTCH1的转录。NOTCH1的过表达增强了SKOV3和OVC1细胞的增殖和上皮-间质转化。此外，NOTCH1激活了NF-κB/ Snail信号传导。最后，在体内实验证明，GClnc1敲低抑制SKOV3的生长和转移，并OVC1细胞在体内。

结论

GClnc1通过募集FOXC2促进NOTCH1转录，从而激活NF-κB/ Snail信号传导并促进EOC细胞的生长和转移。