title: The oncogenic RNA-binding protein Musashi1 is regulated by tumor suppressor miRNAs.
abstract: Musashi1 (Msi1) is an evolutionarily conserved RNA-binding protein that has been implicated in processes like stem cell fate, nervous system development, and tumorigenesis via its activities as a specific regulator of translation. While Msi1 is barely detected in normal adult tissue, it has been observed to be highly expressed in numerous tumor types (e.g. breast, colon, medulloblastoma, glioblastoma, and et cetera). Unfortunately, the molecular cues that are responsible for Msi1 upregulation in cancer cells are largely unknown. Tumor suppressor microRNAs (miRNAs) are known for targeting genes with oncogenic properties like Msi1 and for being either downregulated or deleted in tumor tissue. We observed that Msi1 long 3'UTR region is potentially targeted by several tumor suppressor miRNAs (miR-34a, -101, -128, -137, and -138). Western blotting of endogenous Msi1 protein as well as luciferase assays confirmed Msi1 regulation by these tumor suppressor miRNAs. Furthermore, we observed when examining different cellular states that these miRNAs and Msi1 have opposite expression profiles. Cell proliferation inhibition induced by the tumor suppressor miRNAs was partially rescued by Msi1 transgenic expression. We conclude that tumor suppressor miRNAs are direct and influential regulators of Msi1, affecting its expression pattern during tumorigenesis of malignant nervous system tumors.
authors: Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors: Dat T
authors: DT
authors: Vo
authors: Mei
authors: M
authors: Qiao
authors: Andrew D
authors: AD
authors: Smith
authors: Suzanne C
authors: SC
authors: Burns
authors: Andrew J
authors: AJ
authors: Brenner
authors: Luiz O F
authors: LO
authors: Penalva
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; C491297:MSI1 protein, human; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins