RT Journal Article
SR Electronic
T1 Human Antigen R Binding and Regulation of SOX2 mRNA in Human Mesenchymal Stem Cells
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 243
OP 252
DO 10.1124/mol.115.100701
VO 89
IS 2
A1 Latorre, Elisa
A1 Carelli, Stephana
A1 Caremoli, Filippo
A1 Giallongo, Toniella
A1 Colli, Mattia
A1 Canazza, Alessandra
A1 Provenzani, Alessandro
A1 Di Giulio, Anna Maria
A1 Gorio, Alfredo
YR 2016
UL http://molpharm.aspetjournals.org/content/89/2/243.abstract
AB 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.