Determining the Role of ATP6V0E1 of the Vacuolar-ATPase in Regulating Neuroblastoma Cell Survival and Differentiation
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Neuroblastoma is one of the leading causes of cancer-related childhood deaths. Neuroblastoma arises from the developing sympathetic nervous system where neural crest cells fail to complete the differentiation process. The failure in the differentiation process stimulated the investigation into differentiation-inducing agents capable of activating endogenous differentiation pathways. A high-throughput morphological screen was performed using a library of microRNA mimics to test if microRNA treatment was sufficient to induce neural cell differentiation. The screen identified microRNA 506-3p (miRNA-506) to be a potent tumor suppressor and neuroblastoma cell differentiation inducer. A gene expression array of neuroblastoma cells treated with miR-506 determined that the gene ATP6V0E1 is directly targeted by miRNA-506 and was the most differentially modulated gene from the list, suggesting it plays a role in mediating the function of miRNA-506 in neuroblastoma cells. The objective of this work was to investigate whether ATP6V0E1 plays a role in regulating neuroblastoma cell survival and differentiation. We observed that by using siRNAs to knock down the expression of the e subunit we were able to reduce neuroblastoma proliferation and cell viability. Knockdown of the e subunit was not sufficient to induce neural cell differentiation. These results suggest that the e submit is essential for neuroblastoma cell survival and does not play a role in the neural cell differentiation process. The e submit has been shown to be essential for normal V-ATPase function. This evidence suggest that by knocking down the e submit, V-ATPase efficiency is reduced and the neuroblastoma cells are not able to survive under these conditions.