Proteomics investigation of Nucleostemin role in Nucleo-phosmin mutated OCI-AML 3 cell line

Nucleostemin (NS; product of the GNL3 gene) is a nucleolar/nucleoplasm shuttling GTPase whose levels are high in stem cells while rapidly decreasing upon differentiation. NS levels are also high in several solid and hematological neoplasms, including acute myeloid leukemia (AML). While a role in telomere maintenance, response to stress stimuli and in favoring DNA repair has been proposed in solid cancers, little or no information is available as to the role of nucleostemin in AML. Here we investigate this issue with a proteomics approach. We use as a model system the OCI-AML 3 cell line harboring a heterozygous mutation at the NPM1 gene, which is the most frequent driver mutation in AML (approximately 30% of total AML cases). We show that NS is highly expressed in this cell line but, contrary to what previously shown in other cancers, its presence is dispensable for cell growth and viability. However, proteomics analysis of OCI-AML 3 cell line before and after nu-cleostemin (NS) silencing showed several effects in different biological functions as highlighted by ingenuity pathway analysis (IPA). In particular, we report an effect in down-regulating DNA repair through homologous recombination and we confirmed higher DNA damage rate in OCI-AML 3 cells when NS is depleted, which considerably increases upon stress induced by the topoisomerase II inhibitor etoposide.