Previously, the novel oestrogen (E2)-upregulated lncRNA TC0101441, was identified by us, via microarray analysis. However, the detailed mechanism by which E2 upregulates TC0101441 and the role of TC0101441 in epithelial ovarian cancer (EOC) progression have not been elucidated. In the present study, we further analysed TC0101441, which we designated oestrogen-induced long non-coding RNA-1 (ElncRNA1). We showed that E2 transcriptionally upregulates ElncRNA1 through the oestrogen receptor alpha (ER alpha)-oestrogen response element (ERE) pathway using RNA stability assays, bioinformatics-based searches for ERE binding sites, chromatin immunoprecipitation (ChIP) assays and dual luciferase reporter assays. Clinically, ElncRNA1 levels are significantly higher in EOC tissues than in normal ovarian surface epithelium. In vitro and in vivo loss-of-function assays revealed that ElncRNA1 promotes EOC cell proliferation. This pro-proliferation effect of ElncRNA1 was partially mediated by the regulation of CDK4, CDK6 and cyclin D1. These findings provide the first evidence that E2 upregulates ElncRNA1 at the transcriptional level through the ER alpha-ERE pathway and that this novel E2-upregulated lncRNA has an oncogenic role in EOC growth. The placement of ElncRNA1 in the E2-ER alpha-ERE signalling pathway may provide greater insight into the effects of oestrogen on EOC progression from the perspective of lncRNA.
[1]Fudan Univ, Obstet & Gynecol Hosp, Dept Gynecol, 419 Fangxie Rd, Shanghai 200011, Peoples R China.
[2]Fudan Univ, Shanghai Med Coll, Dept Obstet & Gynecol, Shanghai 200032, Peoples R China.
[3]Shanghai Key Lab Female Reprod Endocrine Related, Shanghai 200011, Peoples R China.
(8.0+极速模式)