Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Coupled miR-155 Deficiency and Hypoxia Lead to the Upregulation of SLC2A3 (GLUT3) and VEGFA in the Leukemic B-cells

Version 1 : Received: 28 April 2023 / Approved: 29 April 2023 / Online: 29 April 2023 (03:34:08 CEST)

How to cite: Golovina, E.; Heizer, T.; Daumova, L.; Bajecny, M.; Savvulidi Vargova, K. Coupled miR-155 Deficiency and Hypoxia Lead to the Upregulation of SLC2A3 (GLUT3) and VEGFA in the Leukemic B-cells. Preprints 2023, 2023041197. https://doi.org/10.20944/preprints202304.1197.v1 Golovina, E.; Heizer, T.; Daumova, L.; Bajecny, M.; Savvulidi Vargova, K. Coupled miR-155 Deficiency and Hypoxia Lead to the Upregulation of SLC2A3 (GLUT3) and VEGFA in the Leukemic B-cells. Preprints 2023, 2023041197. https://doi.org/10.20944/preprints202304.1197.v1

Abstract

Hypoxia represents one of the key factors that stimulate the growth of leukemic cells in their niche. Leukemic cells in hypoxia are forced to reprogram their original transcriptome, miRNome, and metabolome. How the coupling of miRNAs/mRNAs helps to maintain or progress the leukemic status is still not fully described. MicroRNAs (miRNAs) regulate practically all biological processes within cells and play a crucial role in leukemia development/progression. Here we worked with the human cell line MEC-1 (human chronic lymphocytic leukemia (CLL)) where we deleted mature miR-155 by CRISPR/Cas9. MEC-1 cells in hypoxia showed a higher proliferation rate with a relatively low level of apoptosis. Interestingly, miR-155 deficiency decreased the proliferation rate in both, normoxia and hypoxia. Besides common hypoxia-related genes (HIF1α, EGLN1, VHL, HK1, and HK2), we also measured, genes for glucose transporters SLC2A1 (GLUT1) and SLC2A3 (GLUT3). Surprisingly, only SLC2A3 (GLUT3) showed significant overexpression in hypoxia conditions in miR-155 deficient MEC-1cells which points to the possible novel target of miR-155 in CLL. Increased glucose uptake and decreased lactate support our hypothesis that miR-155 deficiency and hypoxia transform cell metabolism. To conclude, miR-155 deficiency and hypoxia-impaired glucose metabolism stimulate GLUT3 in CLL cells.

Keywords

B-cells, hypoxia, miRNA, CRISPR/Cas9, leukemia, gene expression, cell viability

Subject

Biology and Life Sciences, Biology and Biotechnology

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