Abstract
Many facets of the tumor biology of medulloblastoma (MB) have not been fully elucidated. Collapsin response mediator protein 1 (CRMP1) is a member of cytoplasmic family of proteins that regulate the development of central nervous system. Recent studies demonstrated that CRMP1 could function as an invasion suppressor. We reported previously that high mobility group AT-hook 1 (HMGA1) contributed to development of MB and regulated its growth and migration/invasion. Transcriptional profiling and quantitative RT-PCR revealed increased expression of CRMP1 in HMGA1-depleted cells, suggesting that CRMP1 may be a downstream target of HMGA1 in MB. In this study, we showed HMGA1 can bind CRMP1 promoter by chromatin immunoprecipitation (ChIP) assay. Luciferase assay demonstrated a marked enhancement of CRMP1 transcription activity in HMGA1-depleted cells. Furthermore, quantitative RT-PCR revealed a negative correlation between HMGA1 and CRMP1 in 32 MB samples. To investigate the biological roles of CRMP1 in MB pathogenesis, we established MB clones stably expressing CRMP1. Functional analysis revealed that expression of CRMP1 significantly inhibited proliferation, migration, invasion and formation of filopodia and intense stress fiber of MB cells. Our data suggest that HMGA1 regulates CRMP1 expression and CRMP1 is implicated in MB pathogenesis.
Highlights
Medulloblastoma (MB) is the most common malignant central nervous system neoplasm of children
By quantitative RT-PCR, we confirmed that Collapsin response mediator protein 1 (CRMP1) was upregulated in HMGA1-depleted DAOY cells [28]
CRMP1 expression is significantly downregulated compared to adjacent normal tissue [39]
Summary
Medulloblastoma (MB) is the most common malignant central nervous system neoplasm of children. With current multimodal treatment comprised of surgical resection, radiotherapy and chemotherapy, outcome of average risk patient is satisfactory, achieving an around 90% in five year overall survival [2]. What was once thought of as a single disease can be categorized into four principal subgroups, namely, WNT, SHH, Group 3, and Group 4 [6,7,8,9,10]. Each of these subgroup is characterized by distinct transcription signature, chromosomal aberration, demographic features, and clinical outcomes
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