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

Wu, Kun; Guo, Chong; Li, Yixun; Yang, Jing; Zhou, Qiang; Cheng, Shenju; Li, Yanhong; Nie, Bo; Zeng, Yun

doi:10.3892/etm.2021.10503

Cited by 7 publications

(4 citation statements)

References 42 publications

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“…Of course, more experiments are needed to confirm this. However, in the study of Wu et al [39], we find that miR-18a-5p is lowly expressed in doxorubicin-resistant human leukemia strain K562/ADR, which is different from Computational and Mathematical Methods in Medicine our findings. This also suggests that miR-18a-5p may play different biological effects in different diseases, so we need to analyze the specific mechanism of miR-18a-5p and ATM in ESCC as soon as possible.…”

Section: Discussioncontrasting

confidence: 99%

miR-18a-5p and ATM Expression in Esophageal Squamous Cell Carcinoma and Their Correlations with Clinicopathological Features

Fan

2022

Computational and Mathematical Methods in Medicine

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Objective. To investigate miR-18a-5p and ataxia telangiectasia muted (ATM) expression in esophageal squamous cell carcinoma (ESCC) and their correlations with clinicopathological features. Methods. The subjects of this study were 62 ESCC patients (research group, RG) and 57 healthy controls (control group, CG) presented to our hospital between July 2019 and April 2020. Peripheral blood (PB) miR-18a-5p and ATM levels in these participants were quantified via qRT-PCR, and the correlations of the two genes with ESCC patients’ clinicopathological characteristics were investigated. In addition, a two-year follow-up was performed on ESCC patients to understand their survival, so as to further determine the prognostic utility of miR-18a-5p and ATM in ESCC. Factors influencing patient outcomes were identified by COX analysis. Results. PB miR-18a-5p expression was higher in RG compared with CG, while ATM was lower, suggesting an inverse connection between the two genes in ESCC ( P < 0.001 ). miR-18a-5p and ATM levels were determined to be strongly linked to TNM stage, differentiation degree, and lymph node metastasis in ESCC patients ( P < 0.001 and P = 0.007 ). The patients who succumbed to the disease exhibited higher miR-18a-5p and lower ATM than the survival ( P < 0.05 ). ROC analysis suggested favorable evaluation effects of miR-18a-5p and ATM on the occurrence and prognostic death of ESCC ( P < 0.001 ). Further, these two genes were identified by the COX analysis to be factors independently affecting the prognosis of ESCC. Conclusion. miR-18a-5p is highly expressed in ESCC, and ATM is underexpressed, both of which are closely linked to the pathological process of ESCC and have a good evaluation effect on the occurrence and prognosis of ESCC, which may become a breakthrough in future diagnosis and treatment of ESCC.

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Section: Discussioncontrasting

confidence: 99%

miR-18a-5p and ATM Expression in Esophageal Squamous Cell Carcinoma and Their Correlations with Clinicopathological Features

Fan

2022

Computational and Mathematical Methods in Medicine

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“…Particularly in K562 cells, the expression level of miR-18a-5p in DOX-resistant cells is lower compared to K562 cells and normal lymphocytes, and strikingly, miR-18a-5p can inhibit the expression of HIF-1α and, in turn, induce a reduction in the production of pyruvate, ATP and affect the expression of GLUT1, HK-II, PKM2, and lactate dehydrogenase A (LDHA) (Wu et al, 2021).…”

Section: Figurementioning

confidence: 99%

Plant-derived extracts and metabolic modulation in leukemia: a promising approach to overcome treatment resistance

Arévalo

Cruz-Rodríguez

Quijano

et al. 2023

Front. Mol. Biosci.

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Leukemic cells acquire complex and often multifactorial mechanisms of resistance to treatment, including various metabolic alterations. Although the use of metabolic modulators has been proposed for several decades, their use in clinical practice has not been established. Natural products, the so-called botanical drugs, are capable of regulating tumor metabolism, particularly in hematopoietic tumors, which could partly explain the biological activity attributed to them for a long time. This review addresses the most recent findings relating to metabolic reprogramming—Mainly in the glycolytic pathway and mitochondrial activity—Of leukemic cells and its role in the generation of resistance to conventional treatments, the modulation of the tumor microenvironment, and the evasion of immune response. In turn, it describes how the modulation of metabolism by plant-derived extracts can counteract resistance to chemotherapy in this tumor model and contribute to the activation of the antitumor immune system.

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“…Interestingly, imatinib-resistant CML cells were shown to exhibit non-hypoxic upregulation of HIF1α and its target genes, resulting in upregulation of glycolytic processes, increased glucose uptake and lactate production ( 106 ). Recently, it was suggested that activation of glycolytic metabolism in CML cells may be facilitated by reduced expression of miR-18a-5p, which targets the 3’-UTR of HIF1α and leads to HIF1α downregulation in normal hematopoietic cells ( 107 ). In line with a relevant function of HIF1α in resistance to imatinib, it was shown that although imatinib partly inhibits HIF1α expression and transcriptional activity, HIF1α residual function is sufficient to suppress imatinib-induced apoptosis of CML cells ( 85 ).…”

Section: Hifs and Hypoxia Signaling In Leukemiamentioning

confidence: 99%

Hypoxic stress and hypoxia-inducible factors in leukemias

Magliulo

Bernardi

2022

Front. Oncol.

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To cope with hypoxic stress, ancient organisms have developed evolutionally conserved programs centered on hypoxia-inducible transcriptional factors (HIFs). HIFs and their regulatory proteins have evolved as rheostats to adapt cellular metabolism to atmospheric oxygen fluctuations, but the amplitude of their transcriptional programs has tremendously increased along evolution to include a wide spectrum of physiological and pathological processes. The bone marrow represents a notable example of an organ that is physiologically exposed to low oxygen levels and where basal activation of hypoxia signaling appears to be intrinsically wired within normal and neoplastic hematopoietic cells. HIF-mediated responses are mainly piloted by the oxygen-labile α subunits HIF1α and HIF2α, and current literature suggests that these genes have a functional specification that remains to be fully defined. Since their identification in the mid 90s, HIF factors have been extensively studied in solid tumors, while their implication in leukemia has lagged behind. In the last decades however, many laboratories have addressed the function of hypoxia signaling in leukemia and obtained somewhat contradictory results. Suppression of HIFs expression in different types of leukemia has unveiled common leukemia-promoting functions such as stimulation of bone marrow neoangiogenesis, maintenance of leukemia stem cells and chemoresistance. However, genetic studies are revealing that a definition of HIF factors as bona fide tumor promoters is overly simplistic, and, depending on the leukemia subtype, the specific oncogenic event, or the stage of leukemia development, activation of hypoxia-inducible genes may lead to opposite consequences. With this article we will provide an updated summary of the studies describing the regulation and function of HIF1α and HIF2α in blood malignancies, spanning from acute to chronic, lymphoid to myeloid leukemias. In discussing these data, we will attempt to provide plausible explanations to contradictory findings and point at what we believe are areas of weakness in which further investigations are urgently needed. Gaining additional knowledge into the role of hypoxia signaling in leukemia appears especially timely nowadays, as new inhibitors of HIF factors are entering the clinical arena for specific types of solid tumors but their utility for patients with leukemia is yet to be determined.

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

Cited by 7 publications

References 42 publications

miR-18a-5p and ATM Expression in Esophageal Squamous Cell Carcinoma and Their Correlations with Clinicopathological Features

miR-18a-5p and ATM Expression in Esophageal Squamous Cell Carcinoma and Their Correlations with Clinicopathological Features

Plant-derived extracts and metabolic modulation in leukemia: a promising approach to overcome treatment resistance

Hypoxic stress and hypoxia-inducible factors in leukemias

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