Emerging roles of aerobic glycolysis in breast cancer

Wu, Zhi‐Ying; Wu, Jingbo; Zhao, Qijie; Fu, Shaozhi; Jin, Juan

doi:10.1007/s12094-019-02187-8

Cited by 178 publications

(121 citation statements)

References 171 publications

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“…Multiple pathological factors participate in the tumor progression of BC, moreover, circRNA could regulate the series of tumor phenotype, including metastasis and Warburg effect 20 . Warburg effect, also known as the aerobic glycolysis, provides the major energy for the BC tumor microenvironment 21,22 . Warburg effect is characterized by a vital metabolic event involved in proliferation, invasion, and migration in BC 23,24 .…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1α/HK2

et al. 2020

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Compelling evidence has demonstrated the potential functions of circular RNAs (circRNAs) in breast cancer (BC) tumorigenesis. Nevertheless, the underlying mechanism by which circRNAs regulate BC progression is still unclear. The purpose of present research was to investigate the novel circRNA circRNF20 (hsa_circ_0087784) and its role in BC. CircRNA microarray sequencing revealed that circRNF20 was one of the upregulated transcripts in BC samples. Increased circRNF20 level predicted the poor clinical outcome in BC specimens. Functionally, circRNF20 promoted the proliferation and Warburg effect (aerobic glycolysis) of BC cells. Mechanistically, circRNF20 harbor miR-487a, acting as miRNA sponge, and then miR-487a targeted the 3'-UTR of hypoxia-inducible factor-1α (HIF-1α). Moreover, HIF-1α could bind with the promoter of hexokinase II (HK2) and promoted its transcription. In conclusion, this finding illustrates the vital roles of circRNF20 via the circRNF20/ miR-487a/HIF-1α/HK2 axis in breast cancer progress and Warburg effect, providing an interesting insight for the BC tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1α/HK2

et al. 2020

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“…In recent years, increasing evidence indicates that glycolysis plays an important role in the development of inflammation [ 23 , 24 ]. Glycolysis, a ubiquitous metabolic pathway in mammals, is regulated by multiple glycolytic enzymes, including phosphofructokinase (PFK) and pyruvate kinase (PK) [ 25 , 26 ]. Activation of the glycolytic pathway provides essential biomacromolecules, including amino acids and fatty acids, to synthesize inflammatory mediators in cells.…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Property of the Essential Oil from Cinnamomum camphora (Linn.) Presl Leaves and the Evaluation of Its Underlying Mechanism by Using Metabolomics Analysis

et al. 2020

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Cinnamomum camphora (Linn.) Presl has been widely used in traditional Chinese medicine for a variety of purposes. Our previous study indicated the antibacterial mechanism of the essential oil (EO) from C. camphora leaves; however, its anti-inflammatory activity and the underlying mechanism have not been clearly demonstrated. Thus, the present study investigated its anti-inflammatory property. Our data revealed that EO significantly decreased the release of nitric oxide (NO) and the mRNA expression of inducible NO synthase (iNOS) in lipopolysaccharide (LPS)-induced BV2 microglial cells. EO also attenuated LPS-induced increase in the mRNA expression and secretion of inflammatory cytokines including interleukin-6 (IL-6), IL-18, IL-1β and tumor necrosis factor-α (TNF-α). Furthermore, the metabolic profiles of LPS-induced BV2 microglial cells treated with or without EO were explored. Thirty-nine metabolites were identified with significantly different contents, including 21 upregulated and 18 downregulated ones. Five pathways were enriched by shared differential metabolites. Compared with the control cells, the glucose level was decreased, while the lactate level was increased, in the culture supernatant from LPS-stimulated cells, which were reversed by EO treatment. Moreover, compared to the LPS-treated group, the activities of phosphofructokinase (PFK) and pyruvate kinase (PK) in EO group were decreased. In summary, the current study demonstrated that EO from C. camphora leaves acts as an anti-inflammatory agent, which might be mediated through attenuating the glycolysis capacity of microglial cells.

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“…Previous studies have demonstrated the crucial role glycolysis plays in the growth, survival, and metastasis of various human cancers, including breast cancer [1,34,35]. In particular, glycolysis plays an important role in the survival and metastasis of triple-negative breast cancer (TNBC) [34,[36][37][38], an aggressive type of breast cancer with a poor prognosis [39], as well as NSCLC [40,41].…”

Section: Gracillin Inhibits Cellular Bioenergetics By Disrupting Bothmentioning

confidence: 99%

Potent Anticancer Effect of the Natural Steroidal Saponin Gracillin Is Produced by Inhibiting Glycolysis and Oxidative Phosphorylation-Mediated Bioenergetics

Min

Pei

Hyun

et al. 2020

Cancers

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Metabolic rewiring to utilize aerobic glycolysis is a hallmark of cancer. However, recent findings suggest the role of mitochondria in energy generation in cancer cells and the metabolic switch to oxidative phosphorylation (OXPHOS) in response to the blockade of glycolysis. We previously demonstrated that the antitumor effect of gracillin occurs through the inhibition of mitochondrial complex II-mediated energy production. Here, we investigated the potential of gracillin as an anticancer agent targeting both glycolysis and OXPHOS in breast and lung cancer cells. Along with the reduction in adenosine triphosphate (ATP) production, gracillin markedly suppresses the production of several glycolysis-associated metabolites. A docking analysis and enzyme assay suggested phosphoglycerate kinase 1 (PGK1) is a potential target for the antiglycolytic effect of gracillin. Gracillin reduced the viability and colony formation ability of breast cancer cells by inducing apoptosis. Gracillin displayed efficacious antitumor effects in mice bearing breast cancer cell line or breast cancer patient-derived tumor xenografts with no overt changes in body weight. An analysis of publicly available datasets further suggested that PGK1 expression is associated with metastasis status and poor prognosis in patients with breast cancer. These results suggest that gracillin is a natural anticancer agent that inhibits both glycolysis and mitochondria-mediated bioenergetics.

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Emerging roles of aerobic glycolysis in breast cancer

Cited by 178 publications

References 171 publications

Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1α/HK2

Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1α/HK2

Anti-Inflammatory Property of the Essential Oil from Cinnamomum camphora (Linn.) Presl Leaves and the Evaluation of Its Underlying Mechanism by Using Metabolomics Analysis

Potent Anticancer Effect of the Natural Steroidal Saponin Gracillin Is Produced by Inhibiting Glycolysis and Oxidative Phosphorylation-Mediated Bioenergetics

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