title: H19 lncRNA mediates 17β-estradiol-induced cell proliferation in MCF-7 breast cancer cells.
abstract: Estrogen plays a critical role in breast cancer development and progression. However, the mechanism involved in the promotion of breast cancer development and progression by estrogen remains unclear although it has been intensively studied. In the present study, we investigated the estrogen inducibility and functional significance of H19 lncRNA in breast cancer cells and tumor tissues. The screening of 83 disease-related long non-coding RNAs (lncRNAs) revealed that H19 lncRNA was much higher in estrogen receptor (ER)-positive MCF-7 breast cancer cells than in ER-negative MDA-MB-231 cells. 17β-estradiol produced a dose- and time-dependent induction of H19 expression in MCF-7 cells, which was mediated via ERα as evident by the blockade of this 17β-estradiol effect with ICI 182780, a specific ER antagonist and knockdown of ERα using specific RNAi. Moreover, knockdown of H19 lncRNA decreased cell survival and blocked estrogen-induced cell growth while overexpression of H19 lncRNA stimulated cell proliferation. Quantitation of H19 lncRNA in human breast cancer tissues showed that the level of H19 lncRNA was >10-fold higher in ER-positive than in ER-negative tumor tissues. These results suggest that H19 is an estrogen-inducible gene and plays a key role in cell survival and in estrogen-induced cell proliferation in MCF-7 cells, indicating that H19 lncRNA may serve as a biomarker for breast cancer diagnosis and progression, and as a valuable target for breast cancer therapy.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital and Institute of Clinical Pharmacology, Central South University, and Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 410078, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital and Institute of Clinical Pharmacology, Central South University, and Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 410078, P.R. China.
authors.forename: Guo
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital and Institute of Clinical Pharmacology, Central South University, and Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 410078, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital and Institute of Clinical Pharmacology, Central South University, and Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 410078, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital and Institute of Clinical Pharmacology, Central South University, and Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 410078, P.R. China.
authors.forename: Qiong-Ni
authors.initials: QN
authors.lastname: Zhu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital and Institute of Clinical Pharmacology, Central South University, and Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 410078, P.R. China.
authors.forename: Tai-Lin
authors.initials: TL
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Provincial Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Jia-Qin
authors.initials: JQ
authors.lastname: Cai
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital and Institute of Clinical Pharmacology, Central South University, and Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 410078, P.R. China.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital and Institute of Clinical Pharmacology, Central South University, and Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 410078, P.R. China.
authors.forename: Yuan-Shan
authors.initials: YS
authors.lastname: Zhu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival; D004958:Estradiol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D047628:Estrogen Receptor alpha; C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D004958:Estradiol