title: The oncogenic RNA-binding protein Musashi1 is regulated by HuR via mRNA translation and stability in glioblastoma cells.
abstract: Musashi1 (Msi1) is an evolutionarily conserved RNA-binding protein (RBP) that has profound implications in cellular processes such as stem cell maintenance, nervous system development, and tumorigenesis. Msi1 is highly expressed in many cancers, including glioblastoma, whereas in normal tissues, its expression is restricted to stem cells. Unfortunately, the factors that modulate Msi1 expression and trigger high levels in tumors are largely unknown. The Msi1 mRNA has a long 3' untranslated region (UTR) containing several AU- and U-rich sequences. This type of sequence motif is often targeted by HuR, another important RBP known to be highly expressed in tumor tissue such as glioblastoma and to regulate a variety of cancer-related genes. In this report, we show an interaction between HuR and the Msi1 3'-UTR, resulting in a positive regulation of Msi1 expression. We show that HuR increased MSI1 mRNA stability and promoted its translation. We also present evidence that expression of HuR and Msi1 correlate positively in clinical glioblastoma samples. Finally, we show that inhibition of cell proliferation, increased apoptosis, and changes in cell-cycle profile as a result of silencing HuR are partially rescued when Msi1 is ectopically expressed. In summary, our results suggest that HuR is an important regulator of Msi1 in glioblastoma and that this regulation has important biological consequences during gliomagenesis.
authors.affiliation: Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Dat T
authors.initials: DT
authors.lastname: Vo
authors.forename: Kotb
authors.initials: K
authors.lastname: Abdelmohsen
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martindale
authors.forename: Mei
authors.initials: M
authors.lastname: Qiao
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tominaga
authors.forename: Tarea L
authors.initials: TL
authors.lastname: Burton
authors.forename: Jonathan A L
authors.initials: JA
authors.lastname: Gelfond
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Brenner
authors.forename: Vyomesh
authors.initials: V
authors.lastname: Patel
authors.forename: Daniel
authors.initials: D
authors.lastname: Trageser
authors.forename: Björn
authors.initials: B
authors.lastname: Scheffler
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.forename: Luiz O F
authors.initials: LO
authors.lastname: Penalva
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051959:ELAV Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes / Q000235:genetics; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics*; D020871:RNA Stability / Q000187:drug effects / Q000235:genetics*; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D020413:3' Untranslated Regions; D051959:ELAV Proteins; C491297:MSI1 protein, human; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins