Department of Chemotherapy, Oncology Department, First Affiliated Hospital of Xi'an Jiaotong University, China.
Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Xi'an Jiaotong University, China.
Mol Oncol. 2021 May;15(5):1584-1596. doi: 10.1002/1878-0261.12932. Epub 2021 Mar 19.
Ovarian cancer (OC) is highly prevalent and is associated with high mortality rates due to metastasis and relapse. In this study, we assessed the role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in OC to gain further insight into mechanisms that contribute to its aggressiveness. We analyzed the correlation between SNHG1, miR-454 and zinc finger E-box-binding homeobox 1 (ZEB1) using a dual-luciferase reporter assay. Alterations in cell metastasis and invasiveness were observed using wound-healing and Transwell invasion assays, respectively. Tumor xenografts allowed us to monitor liver metastasis of mice injected with A2780 cells. We found that SNHG1 is overexpressed in OC. Downregulation of SNHG1 promoted miR-454 expression and reduced ZEB1 levels. In addition, knockdown of SNHG1, also reduced the aggressiveness of A2780 and SK-OV3 cells. Furthermore, SNHG1 downregulation by siRNA hindered cell migration and invasion; however, this effect was reversed by co-transfection of miR-454 into A2780 and SK-OV3 cells. Moreover, SNHG1 increased ZEB1 expression by downregulating miR-454 and activated Akt signaling, thereby promoting epithelial-mesenchymal transition and enhancing the invasiveness of OC cells. Tumor xenograft analyses confirmed that SNHG1 affects OC proliferation and metastasis in vivo. In summary, our data demonstrate that SNHG1 plays crucial roles in tumor progression and may be a useful maker for OC prognosis.
卵巢癌(OC)的发病率很高,由于转移和复发,死亡率也很高。在本研究中,我们评估了长非编码 RNA(lncRNA)小核仁 RNA 宿主基因 1(SNHG1)在 OC 中的作用,以更深入地了解其侵袭性的机制。我们使用双荧光素酶报告基因检测分析了 SNHG1、miR-454 和锌指 E 框结合同源盒 1(ZEB1)之间的相关性。通过划痕愈合和 Transwell 侵袭实验分别观察到细胞转移和侵袭能力的改变。肿瘤异种移植使我们能够监测注射 A2780 细胞的小鼠的肝转移。我们发现 SNHG1 在 OC 中过表达。SNHG1 的下调促进了 miR-454 的表达并降低了 ZEB1 水平。此外,SNHG1 的敲低还降低了 A2780 和 SK-OV3 细胞的侵袭性。此外,siRNA 下调 SNHG1 抑制了细胞迁移和侵袭;然而,当将 miR-454 共转染到 A2780 和 SK-OV3 细胞中时,这种作用被逆转。此外,SNHG1 通过下调 miR-454 增加 ZEB1 表达并激活 Akt 信号通路,从而促进上皮间质转化并增强 OC 细胞的侵袭性。肿瘤异种移植分析证实 SNHG1 影响 OC 在体内的增殖和转移。总之,我们的数据表明 SNHG1 在肿瘤进展中起着关键作用,可能是 OC 预后的有用标志物。