Although oestrogen (E2) signalling has long been implicated in epithelial ovarian cancer (EOC) progression, the underlying mechanisms remain unknown. Long noncoding RNAs (lncRNAs) play a major role in cancer progression; therefore, our aim was to explore whether any lncRNA is regulated by E2 and plays some potential roles in the hormonal regulation of EOC progression. Here, we reported that E2 significantly dysregulated 115 lncRNAs (fold change ≥1.5, P<0.05) in E2 receptor (ER) alpha (ERα)-positive EOC SKOV3 cells compared with E2-untreated controls based on the microarray analysis. E2 regulation of the expression of 58 lncRNAs was bioinformatics predicted to be ERα-mediated; this was confirmed for two candidates. Both TC0101441 and TC0101686 were dysregulated by E2 in another ERα-positive PEO1 cells but not in ERα-negative A2780 cells. Additionally, the modulation of TC0101441 and TC0101686 expression by E2 was abrogated by the ER inhibitor ICI 182, 780 and short hairpin RNAs targeting ERα (ERα-shRNA). Further study of the two lncRNA expression indicated that ERα-positive EOC tissues had lower expression of TC0101686 and higher expression of TC0101441 compared to ERα-negative tissues. Particularly, elevated TC0101441 expression was correlated with lymph node metastasis, showing a metastatic potential. Results of in vitro assays further confirmed the pro-metastatic effect of TC0101441 and revealed that knockdown of TC0101441 also impaired E2-induced EOC cell migration/invasion by at least partly, regulating MMP2 and MMP3. Together, our findings demonstrate, for the first time, that E2 modulates lncRNA expression in ERα-positive EOC cells and that this regulation is sometimes ERα-mediated. Furthermore, our findings reveal that TC0101441contributes to E2-induced EOC cell migration/invasion. These results may shed a new insight into estrogenic effect on EOC progression by providing a perspective of lncRNA.
Keywords: ERα; Oestrogen; Ovarian cancer; lncRNA.
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