B23/NPM is a multifunctional
nucleolar protein frequently overexpressed, mutated, or rearranged in neoplastic tissues. B23/NPM is involved in diverse biological processes and is mainly regulated by heteroligomer association and posttranslational modification, phosphorylation being a major posttranslational event. While the role of B23/NPM in supporting and/or driving malignant transformation is widely recognized, the particular relevance of its CK2-mediated phosphorylation remains unsolved. Interestingly, the pharmacologic inhibition of such phosphorylation event by
CIGB-300, a clinical-grade
peptide drug, was previously associated to apoptosis induction in tumor cell lines. In this work, we sought to identify the biological processes modulated by
CIGB-300 in a
lung cancer cell line using subtractive suppression hybridization and subsequent functional annotation clustering. Our results indicate that
CIGB-300 modulates a subset of genes involved in
protein synthesis (ES = 8.4, p < 0.001), mitochondrial
ATP metabolism (ES = 2.5, p < 0.001), and ribosomal biogenesis (ES = 1.5, p < 0.05). The impairment of these cellular processes by
CIGB-300 was corroborated at the molecular and cellular levels by Western blot (P-S6/P-4EBP1, translation), confocal microscopy (JC-1, mitochondrial potential), qPCR (45SrRNA/p21, ribosome biogenesis), and electron microscopy (nucleolar structure, ribosome biogenesis). Altogether, our findings provide new insights on the potential relevance of the CK2-mediated phosphorylation of B23/NPM in
cancer cells, revealing at the same time the potentialities of its pharmacological manipulation for
cancer therapy. Finally, this work also suggests several candidate gene
biomarkers to be evaluated during the clinical development of the anti-CK2
peptide CIGB-300.