title: Effects of oestrogen on long noncoding RNA expression in oestrogen receptor alpha-positive ovarian cancer cells.
abstract: 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.
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China; Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, China; Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai 200011, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of General Surgery, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Lechi
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China; Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, China; Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai 200011, China.
authors.forename: Jingxin
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China; Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, China; Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai 200011, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China; Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, China; Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai 200011, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China; Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, China; Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai 200011, China.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Lv
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China; Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, China; Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai 200011, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China; Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, China; Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai 200011, China. Electronic address: huakeqin@126.com.
authors.forename: Keqin
authors.initials: K
authors.lastname: Hua
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004958:Estradiol / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D062085:RNA, Long Noncoding; D004958:Estradiol; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: ERα; Oestrogen; Ovarian cancer; lncRNA