Musashi1 Enhances Cell Growth and Increases Chemoresistance in Neuroblastoma.

BACKGROUND/AIM: Neuroblastoma remains a major cause of pediatric cancer mortality and although intensive multimodal treatment strategies have improved survival, they have also led to an increased risk of long-term treatment-related toxicities among survivors. This study aimed to evaluate the potential involvement of (Musashi) Msi1 in neuroblastoma oncogenesis and etoposide treatment response.

MATERIALS AND

METHODS

The expression of Msi1, an RNA-binding protein and stem cell marker, was examined in MYCN amplified and non-amplified cells, which were then quantified by densitometry. Immunoblotting was used to assess total protein levels in all cell lines. In addition, the impact of Msi1 silencing on etoposide sensitivity was also assessed.

RESULTS

The study found that increased Msi1 expression is associated with MYCN-amplification and, in a publicly available clinical database, Msi1 upregulation correlates with decreased overall survival and is seen in older patients and those with more advanced disease. Furthermore, in vitro silencing of Msi1 was associated with decreased cell proliferation and colony formation, as well as increased sensitivity to etoposide treatment. These changes correlated with altered expression of several cell cycle, proliferation, and DNA damage repair genes that are known Msi1 targets in other malignancies.

CONCLUSION

These findings indicate that Msi1 could serve as a novel therapeutic target for high-risk, treatment-refractory neuroblastoma.