Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Acta Biochim Biophys Sin (Shanghai). 2019 Sep 6;51(9):953-959. doi: 10.1093/abbs/gmz085.
LncRNA MIR4435-2HG is characterized as an oncogene in lung cancer. However, its role in ovarian carcinoma (OC) is unclear. In this study, we aimed to investigate the role of MIR4435-2HG in OC. We found that both MIR4435-2HG and transforming growth factor beta 1 (TGF-β1) were upregulated in OC. MIR4435-2HG is associated with tumor metastasis but not with tumor size. Upregulation of MIR4435-2HG distinguished early stage (Stage I and II) OC patients from healthy controls. Correlation analysis showed that plasma levels of MIR4435-2HG and TGF-β1 were positively correlated only in OC patients. qPCR and western blot analysis results showed that MIR4435-2HG overexpression led to upregulation of TGF-β1 in OC cells, while TGF-β1 treatment did not significantly affect MIR4435-2HG expression. Transwell invasion and migration assays showed that MIR4435-2HG and TGF-β1 promoted the invasion and migration of OC cells while TGF-β inhibitor suppressed the invasion and migration of these cells. Further analysis of the Transwell invasion and migration assay results showed that TGF-β inhibitor reduced the effects of MIR4435-2HG overexpression. Therefore, our results suggested that lncRNA MIR4435-2HG may promote OC by upregulating TGF-β1. Further characterization of the functions of MIR4435-2HG in OC may provide novel targets for cancer therapies.
长链非编码 RNA MIR4435-2HG 在肺癌中被表征为一种癌基因。然而,其在卵巢癌(OC)中的作用尚不清楚。在本研究中,我们旨在研究 MIR4435-2HG 在 OC 中的作用。我们发现 MIR4435-2HG 和转化生长因子β 1(TGF-β1)在 OC 中均上调。MIR4435-2HG 与肿瘤转移有关,但与肿瘤大小无关。MIR4435-2HG 的上调将早期(I 期和 II 期)OC 患者与健康对照者区分开来。相关性分析表明,OC 患者的血浆 MIR4435-2HG 和 TGF-β1 水平仅呈正相关。qPCR 和 Western blot 分析结果表明,MIR4435-2HG 过表达导致 OC 细胞中 TGF-β1 的上调,而 TGF-β1 处理对 MIR4435-2HG 表达没有显著影响。Transwell 侵袭和迁移实验表明,MIR4435-2HG 和 TGF-β1 促进 OC 细胞的侵袭和迁移,而 TGF-β 抑制剂抑制这些细胞的侵袭和迁移。进一步分析 Transwell 侵袭和迁移实验结果表明,TGF-β 抑制剂降低了 MIR4435-2HG 过表达的影响。因此,我们的结果表明,lncRNA MIR4435-2HG 可能通过上调 TGF-β1 促进 OC。进一步表征 MIR4435-2HG 在 OC 中的功能可能为癌症治疗提供新的靶点。