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bioRxiv · 10.1101/2023.03.06.530131

Gene Expression Profiling Unveils the Temporal Dynamics of CIGB-300-Regulated Transcriptome in AML Cells

Vazquez-Blomquist, D.·Ramon, A. C.·Rosales, M.·Perez, G. V.·Rosales, A.·Palenzuela, D.·Perera, Y.·Perea, S. E.
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Abstract

Protein kinase CK2 activity is implicated in the pathogenesis of various hematological malignancies like Acute Myeloid Leukemia (AML) that remains challenging concerning treatment. Consequently, here we used Illumina HT-12 microarray gene RNA expression profiling to study the molecular events that might support the anti-leukemic effect of CIGB-300 peptide which targets both CK2 substrates and the CK2 catalytic subunits on HL-60 and OCI-AML3 cell lines. As a result, 185 and 812 genes appeared significantly modulated in HL-60 cells at 30 min and 3 h of incubation with CIGB-300 for p< 0.01 and FC>[boxv]1.5[boxv], respectively; while 222 and 332 genes appeared modulated in OCI-AML3 cells. Importantly, functional enrichment analysis evidenced that genes and transcription factors related to apoptosis, cell cycle, leukocyte differentiation, signaling by cytokines/interleukins, and NF-kB, TNF signaling pathways were significantly represented in AML cells transcriptomic profiles. The influence of CIGB-300 on these biological processes and pathways is dependent on the cellular background, in first place, and treatment duration. Of note, the impact of the peptide on NF-kB signaling was corroborated by the quantification of selected NF-kB target genes, as well as the measurement of p50 binding activity and soluble TNF- induction. Quantification of CSF1/M-CSF and CDKN1A/P21 by PCR supports peptide effects on differentiation and cell cycle. Overall, here we explore for the first time the temporal dynamics of the gene expression profile regulated by CIGB-300 and provide fresh molecular clues concerning the antineoplastic effect of CIGB-300 in two relevant AML backgrounds.

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Vazquez-Blomquist, D., Ramon, A. C., Rosales, M., Perez, G. V., Rosales, A., Palenzuela, D., Perera, Y., Perea, S. E.. 2023-03-08. Gene Expression Profiling Unveils the Temporal Dynamics of CIGB-300-Regulated Transcriptome in AML Cells. https://doi.org/10.1101/2023.03.06.530131

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