Neuroblastoma is one of the most common childhood cancers with one of the lowest survival rates, accounting for 15% of childhood cancer mortality. Approximately 15% of patients do not respond to initial treatment, and about half of children treated for high-risk neuroblastoma will relapse following remission. Ionizing radiation has long been a standard course of treatment for these tumors; however, resistance to radiation is a poorly understood and highly common issue. We found that two microRNAs with opposite functions were expressed in two different neuroblastoma cell lines with marked differences in radiosensitivity. Tumor suppressor miR-34a and putative oncogene miR-1228 are differentially expressed following radiation exposure. The differences in expression correlate with different radiation sensitivity of SK-N-AS and SK-N-DZ cell lines. Ultimately, cell death and survival of these cell lines depend on expression of tumor suppressor gene TP53 and oncogenes such as MET, MYCN, and BCL2, regulated by one or both of the microRNAs under investigation. Preliminary work also found these microRNAs may be preferentially packaged into extracellular vesicles, such as exosomes, providing a native means of directly altering the cell signaling mechanism and target gene expression. Furthering our understanding of these microRNAs in neuroblastoma may enable us to circumvent acquired treatment resistance of the tumors and increase overall efficacy of the therapies through direct targeting that could alter expression of these downstream genes and enhance the radiation response in neuroblastoma.

Creator

• Ritner, Carissa

DOI

• https://doi.org/10.21985/n2-c651-m578

Subject

• Cellular biology

Language

• en

Alternate Identifier

• etdadmin_upload_977952
• http://dissertations.umi.com/northwestern:16470

Date created

• 2023-01-01

Resource type

• Dissertation

Rights statement

• In Copyright