Department of Obstetrics and Gynecology, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, 362000, Fujian, PR China.
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, PR China.
Exp Cell Res. 2021 Feb 1;399(1):112422. doi: 10.1016/j.yexcr.2020.112422. Epub 2020 Dec 16.
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.
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.
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.
GClnc1 promoted NOTCH1 transcription by recruiting FOXC2, thereby activating the NF-κB/Snail signaling and promoting EOC cell growth and metastasis.
上皮性卵巢癌（EOC）是一种致命性很高的妇科癌症。长链非编码 RNA（lncRNA）胃癌相关 lncRNA1（GClnc1）已被证明在转移中发挥关键作用。因此，本研究旨在探讨 GClnc1 与 EOC 转移和进展的相关性。
首先，收集 57 对 EOC 和癌旁组织，通过 RT-qPCR 检测 GClnc1 的表达。随后，构建沉默/过表达 GClnc1 的 OVC1 和 SKOV3 细胞，检测细胞活性、凋亡、迁移和侵袭能力的变化。然后，通过核/浆分离、ISH 和 FISH 检测 GClnc1 的亚细胞定位。预测并验证 GClnc1 与叉头框蛋白 C2（FOXC2）以及 FOXC2 与 NOTCH1 之间的结合关系。
GClnc1 在 EOC 组织中显著过表达，沉默 GClnc1 可抑制细胞活力并促进细胞凋亡。此外，核内 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-间充质转化。此外，NOTCH1 激活了 NF-κB/Snail 信号通路。最后，体内实验表明，沉默 GClnc1 可抑制 SKOV3 和 OVC1 细胞在体内的生长和转移。
GClnc1 通过募集 FOXC2 促进 NOTCH1 的转录，从而激活 NF-κB/Snail 信号通路，促进 EOC 细胞的生长和转移。
