title: Human Antigen R Binding and Regulation of SOX2 mRNA in Human Mesenchymal Stem Cells.
abstract: Since 2005, sex determining region y-box 2 (SOX2) has drawn the attention of the scientific community for being one of the key transcription factors responsible for pluripotency induction in somatic stem cells. Our research investigated the turnover regulation of SOX2 mRNA in human adipose-derived stem cells, considered one of the most valuable sources of somatic stem cells in regenerative medicine. Mitoxantrone is a drug that acts on nucleic acids primarily used to treat certain types of cancer and was recently shown to ameliorate the outcome of autoimmune diseases such as multiple sclerosis. In addition, mitoxantrone has been shown to inhibit the binding of human antigen R (HuR) RNA-binding protein to tumor necrosis factor-α mRNA. Our results show that HuR binds to the 3'-untranslated region of SOX2 mRNA together with the RNA-induced silencing complex miR145. The HuR binding works by stabilizing the interaction between the 3'-untranslated region and the RNA-induced silencing complex. Cell exposure to mitoxantrone leads to HuR detachment and the subsequent prolongation of the SOX2 mRNA half-life. The prolonged SOX2 half-life allows improvement of the spheroid-forming capability of the adipose-derived stem cells. The silencing of HuR confirmed the above observations and illustrates how the RNA-binding protein HuR may be a required molecule for regulation of SOX2 mRNA decay.
authors.affiliation: Laboratory of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy (E.L., S.C., F.C., T.G., M.C., A.M.D.G., A.G.); Laboratory of Cell Biology, Cerebrovascular Diseases Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy (A.C.); and Laboratory of Genomic Screening Center for Integrative Biology, University of Trento, Trento, Italy (A.P.) stephana.carelli@guest.unimi.it elisa.latorre@unimi.it.
authors.forename: Elisa
authors.initials: E
authors.lastname: Latorre
authors.affiliation: Laboratory of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy (E.L., S.C., F.C., T.G., M.C., A.M.D.G., A.G.); Laboratory of Cell Biology, Cerebrovascular Diseases Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy (A.C.); and Laboratory of Genomic Screening Center for Integrative Biology, University of Trento, Trento, Italy (A.P.) stephana.carelli@guest.unimi.it elisa.latorre@unimi.it.
authors.forename: Stephana
authors.initials: S
authors.lastname: Carelli
authors.affiliation: Laboratory of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy (E.L., S.C., F.C., T.G., M.C., A.M.D.G., A.G.); Laboratory of Cell Biology, Cerebrovascular Diseases Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy (A.C.); and Laboratory of Genomic Screening Center for Integrative Biology, University of Trento, Trento, Italy (A.P.).
authors.forename: Filippo
authors.initials: F
authors.lastname: Caremoli
authors.affiliation: Laboratory of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy (E.L., S.C., F.C., T.G., M.C., A.M.D.G., A.G.); Laboratory of Cell Biology, Cerebrovascular Diseases Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy (A.C.); and Laboratory of Genomic Screening Center for Integrative Biology, University of Trento, Trento, Italy (A.P.).
authors.forename: Toniella
authors.initials: T
authors.lastname: Giallongo
authors.affiliation: Laboratory of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy (E.L., S.C., F.C., T.G., M.C., A.M.D.G., A.G.); Laboratory of Cell Biology, Cerebrovascular Diseases Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy (A.C.); and Laboratory of Genomic Screening Center for Integrative Biology, University of Trento, Trento, Italy (A.P.).
authors.forename: Mattia
authors.initials: M
authors.lastname: Colli
authors.affiliation: Laboratory of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy (E.L., S.C., F.C., T.G., M.C., A.M.D.G., A.G.); Laboratory of Cell Biology, Cerebrovascular Diseases Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy (A.C.); and Laboratory of Genomic Screening Center for Integrative Biology, University of Trento, Trento, Italy (A.P.).
authors.forename: Alessandra
authors.initials: A
authors.lastname: Canazza
authors.affiliation: Laboratory of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy (E.L., S.C., F.C., T.G., M.C., A.M.D.G., A.G.); Laboratory of Cell Biology, Cerebrovascular Diseases Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy (A.C.); and Laboratory of Genomic Screening Center for Integrative Biology, University of Trento, Trento, Italy (A.P.).
authors.forename: Alessandro
authors.initials: A
authors.lastname: Provenzani
authors.affiliation: Laboratory of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy (E.L., S.C., F.C., T.G., M.C., A.M.D.G., A.G.); Laboratory of Cell Biology, Cerebrovascular Diseases Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy (A.C.); and Laboratory of Genomic Screening Center for Integrative Biology, University of Trento, Trento, Italy (A.P.).
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Giulio
authors.affiliation: Laboratory of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy (E.L., S.C., F.C., T.G., M.C., A.M.D.G., A.G.); Laboratory of Cell Biology, Cerebrovascular Diseases Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy (A.C.); and Laboratory of Genomic Screening Center for Integrative Biology, University of Trento, Trento, Italy (A.P.).
authors.forename: Alfredo
authors.initials: A
authors.lastname: Gorio
mesh_terms: D002478:Cells, Cultured; D000067780:ELAV-Like Protein 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D012333:RNA, Messenger / Q000502:physiology*; D055748:SOXB1 Transcription Factors / Q000502:physiology*
chemical_list: D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D012333:RNA, Messenger; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors