Musashi I modulates cell proliferation genes in the medulloblastoma cell line Daoy

Background: Musashi I (Msi I) is an RNA binding protein with a central role during nervous system development and stem cell maintenance. High levels of Msi I have been reported in several malignancies including brain tumors thereby associating Msi I and cancer. Methods: We used the human medulloblastoma cell line Daoy as model system in this study to knock down the expression of Msil 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 Msi I depleted Daoy cells. Results: We observed that MSII expression was elevated in Daoy cells cultured as neurospheres compared to those grown as monolayer. These data indicated that Msil might be involved in regulating proliferation in cancer cells. Here we show that shRNA mediated Msi I 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 Msi I knockdown, demonstrating that Msi I modulated the expression of a subset of cell proliferation, differentiation and survival genes in Daoy. Conclusion: Our data suggested that Msi I 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, Msi I might be a positive regulator of tumor progression and a potential target for therapy.