Abstract
BackgroundMusashi1 (Msi1) is an RNA binding protein with a central role during nervous system development and stem cell maintenance. High levels of Msi1 have been reported in several malignancies including brain tumors thereby associating Msi1 and cancer.MethodsWe used the human medulloblastoma cell line Daoy as model system in this study to knock down the expression of Msi1 and determine the effects upon soft agar growth and neurophere formation. Quantitative RT-PCR was conducted to evaluate the expression of cell proliferation, differentiation and survival genes in Msi1 depleted Daoy cells.ResultsWe observed that MSI1 expression was elevated in Daoy cells cultured as neurospheres compared to those grown as monolayer. These data indicated that Msi1 might be involved in regulating proliferation in cancer cells. Here we show that shRNA mediated Msi1 depletion in Daoy cells notably impaired their ability to form colonies in soft agar and to grow as neurospheres in culture. Moreover, differential expression of a group of Notch, Hedgehog and Wnt pathway related genes including MYCN, FOS, NOTCH2, SMO, CDKN1A, CCND2, CCND1, and DKK1, was also found in the Msi1 knockdown, demonstrating that Msi1 modulated the expression of a subset of cell proliferation, differentiation and survival genes in Daoy.ConclusionOur data suggested that Msi1 may promote cancer cell proliferation and survival as its loss seems to have a detrimental effect in the maintenance of medulloblastoma cancer cells. In this regard, Msi1 might be a positive regulator of tumor progression and a potential target for therapy.
Highlights
Musashi1 (Msi1) is an RNA binding protein with a central role during nervous system development and stem cell maintenance
Msi1 expression in Daoy neurosphere cultures To determine if Msi1 might play a role in Daoy cancer cell proliferation, we measured the levels of MSI1 mRNA in Daoy neurosphere cultures by quantitative RT-PCR (Figure 1)
Since neurosphere cultures can be enriched in tumor re-initiating cells and Msi1 is a stem cell marker with a role in cell cycle progression [13], the higher level of Msi1 detected in neurospheres indicated that Msi1 may contribute to Daoy cancer cell proliferation
Summary
Musashi (Msi1) is an RNA binding protein with a central role during nervous system development and stem cell maintenance. Musasi (Msi1) is an RNA binding protein essential during nervous system development. It is considered a stem cell marker whose expression has been found to be conserved across species from fly to human [1]. Binding of Msi to specific motifs located in the 3' untranslated region (UTR) of these mRNAs seems to interfere with translation, thereby decreasing Numb and p21WAF ( known as Cdkn1a) protein levels [12,13]. It is plausible to surmise that by repressing translation of Numb and p21WAF, high levels of Msi might promote aberrant cell proliferation and failure in differentiation and apoptosis
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