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Δευτέρα 30 Αυγούστου 2021

MicroRNA-18a-5p regulates the Warburg effect by targeting hypoxia-inducible factor 1α in the K562/ADM cell line

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Exp Ther Med. 2021 Oct;22(4):1069. doi: 10.3892/etm.2021.10503. Epub 2021 Jul 28.

ABSTRACT

The Warburg effect is involved in drug resistance and recurrence of cancer, and poses a challenge for the treatment of chronic myelogenous leukemia (CML). Hypoxia-inducible factor 1α (HIF-1α) plays a key role in the Warburg effect. microRNAs (miRs) targeting HIF-1α have potential of regulating such aberrant metabolic process. The present study demonstrated that miR-18a-5p was expressed at a low level in K562/ADM cells via reverse transcription-quantitative PCR (RT-qPCR). The results of the luciferase reporter assay indicated that miR-18a-5p could specifically bind the 3'-untranslated region of HIF-1α. Through RT-qPCR and western blotting, it was revealed that miR-18a-5p downregulated the expression of HIF-1α. By inhibiting HIF-1α, miR-18a-5p suppressed aerobic glycolysis in K562/ADM cells, according to the results produced by glucose uptake , lactate production, pyruvate level and ATP synthesis measurement, along with the results obtained from extracellular acidification rate and oxygen consumption rate assays. These results provided new evidence that miR-18a-5p may suppress the Warburg effect by targeting HIF-1α. Furthermore, via CCK-8 and flow cytometry assays, cells transfected with miR-18a-5p mimics were more sensitive to Adriamycin (AMD) compared with AMD group. Reversing the Warburg effect by miR-30a-5p might provide a potential therapeutic strategy for CML.

PMID:34447462 | PMC:PMC8355681 | DOI:10.3892/etm.2021.10503

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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