title: MALAT1 and HOTAIR Long Non-Coding RNAs Play Opposite Role in Estrogen-Mediated Transcriptional Regulation in Prostate Cancer Cells.
abstract: In the complex network of nuclear hormone receptors, the long non-coding RNAs (lncRNAs) are emerging as critical determinants of hormone action. Here we investigated the involvement of selected cancer-associated lncRNAs in Estrogen Receptor (ER) signaling. Prior studies by Chromatin Immunoprecipitation (ChIP) Sequencing showed that in prostate cancer cells ERs form a complex with the endothelial nitric oxide synthase (eNOS) and that in turn these complexes associate with chromatin in an estrogen-dependent fashion. Among these associations (peaks) we focused our attention on those proximal to the regulatory region of HOTAIR and MALAT1. These transcripts appeared regulated by estrogens and able to control ERs function by interacting with ERα/ERβ as indicated by RNA-ChIP. Further studies performed by ChIRP revealed that in unstimulated condition, HOTAIR and MALAT1 were present on pS2, hTERT and HOTAIR promoters at the ERE/eNOS peaks. Interestingly, upon treatment with17β-estradiol HOTAIR recruitment to chromatin increased significantly while that of MALAT1 was reduced, suggesting an opposite regulation and function for these lncRNAs. Similar results were obtained in cells and in an ex vivo prostate organotypic slice cultures. Overall, our data provide evidence of a crosstalk between lncRNAs, estrogens and estrogen receptors in prostate cancer with important consequences on gene expression regulation.
authors.affiliation: National Research Council, Institute of Cell Biology and Neurobiology, Rome, 00143, Italy.|Università Cattolica, Institute of Medical Pathology, Rome, 00168, Italy.
authors.forename: Aurora
authors.initials: A
authors.lastname: Aiello
authors.affiliation: Università Cattolica, Institute of Medical Pathology, Rome, 00168, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Bacci
authors.affiliation: National Research Council, Institute of Cell Biology and Neurobiology, Rome, 00143, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Re
authors.affiliation: Università Cattolica, Institute of Human Physiology, Rome, 00168, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Ripoli
authors.affiliation: Università Cattolica, Institute of Pathology, Rome, 00168, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pierconti
authors.affiliation: Università Cattolica, Fondazione Policlinico 'A. Gemelli', Urological Clinic, Rome, 00168, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pinto
authors.affiliation: Università Cattolica, Multidisciplinary Breast Center, Fondazione Policlinico 'A. Gemelli', Rome, 00168, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Masetti
authors.affiliation: Università Cattolica, Institute of Human Physiology, Rome, 00168, Italy.|San Raffaele Pisana Scientific Institute for Research, Hospitalization and Health Care, 00163 Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Grassi
authors.affiliation: Goethe University Frankfurt, Division of Cardiovascular Epigenetics, Department of Cardiology, Internal Medicine Clinic III, Frankfurt am Main, 60590, Germany.
authors.forename: Carlo
authors.initials: C
authors.lastname: Gaetano
authors.affiliation: Università Cattolica, Fondazione Policlinico 'A. Gemelli', Urological Clinic, Rome, 00168, Italy.
authors.forename: Pier Francesco
authors.initials: PF
authors.lastname: Bassi
authors.affiliation: Università Cattolica, Institute of Medical Pathology, Rome, 00168, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pontecorvi
authors.affiliation: Università Cattolica, Institute of Medical Pathology, Rome, 00168, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Nanni
authors.affiliation: National Research Council, Institute of Cell Biology and Neurobiology, Rome, 00143, Italy.|Goethe University Frankfurt, Internal Medicine Clinic III, Frankfurt am Main, 60590, Germany.
authors.forename: Antonella
authors.initials: A
authors.lastname: Farsetti
mesh_terms: D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D008867:Microtomy; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D020320:Oligoribonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D053766:Presenilin-2 / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D046509:Tissue Culture Techniques; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C561566:HOTAIR long untranslated RNA, human; C557041:MALAT1 long non-coding RNA, human; D020320:Oligoribonucleotides, Antisense; C508861:PSEN2 protein, human; D053766:Presenilin-2; D062085:RNA, Long Noncoding; D004958:Estradiol; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C509186:TERT protein, human; D019098:Telomerase