Long Non-Coding RNA LINC00511 Mediates the Effects of ESR1 on Proliferation and Invasion of Ovarian Cancer Through miR-424-5p and miR-370-5p.

Abstract

IntroductionEstrogen receptor 1 (ESR1) plays an important role in the pathological events of ovarian cancer (OV), but the underlying mechanism is not completely understood. Using bioinformatics analysis, we found that ESR1 is involved in the regulation of some lncRNAs that are highly expressed in ovarian cancer. The lncRNAs might mediate the roles of ESR1 in OV occurrence and progression.MethodsThis study measured the expression of the lncRNAs in OV cell lines using qRT-PCR. Some of the lncRNAs were silenced or overexpressed to determine their effects on the growth and invasion of CAOV3 cells with the stimulation of 17 beta-estradiol or not.ResultsESR1-expressing OV cells (CAOV3 cells) shows higher LINC00511 and RP11-166P13.3 expression than the ESR1-losing OV cells (UWB1.289 cells). Depletion of the two lncRNAs enhanced cell viability and invasion and decreased apoptosis rate. In these respects, effects of LINC00511 were more remarkable than that those of RP11-166P13.3. Treatment with 17 beta-estradiol to stimulate ESR1 increased LINC00511 expression, while ESR1 inhibitor Fulvestrant decreased LINC00511 expression. FISH assay confirmed that LINC00511 is present in the cytoplasm and nucleus. Bioinformatics analysis revealed the interaction of LINC00511 with miR-424-5p and miR-370-5p, which was further identified by RNA-pull down assay. As indicated by RIP assay, silencing LINC00511 increased the interaction between Ago protein and these two miRNAs.DiscussionOur study showed that ESR1-induced upregulation of LINC00511 promoted proliferation and invasion of CAOV3 cells probably through sponging miR-424-5p and miR-370-5p.