Musashi1 modulates cell proliferation genes in the medulloblastoma cell line Daoy.
BACKGROUND
Musashi1 (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.


METHODS
We 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.


RESULTS
We 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.


CONCLUSIONS
Our 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.
Sanchez-Diaz
Patricia C
PC
Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, TX, USA. sanchezdiaz@uthscsa.edu
Burton
Tarea L
TL
Burns
Suzanne C
SC
Hung
Jaclyn Y
JY
Penalva
Luiz O F
LO
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D053823:Hedgehog Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051880:Receptors, Notch / Q000096:biosynthesis / Q000235:genetics; D051153:Wnt Proteins / Q000096:biosynthesis / Q000235:genetics
D053823:Hedgehog Proteins; C491297:MSI1 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051880:Receptors, Notch; D051153:Wnt Proteins