Epigenetic regulation of the Warburg effect by H2B monoubiquitination

Jing, Yuanya; Cai, Fengfeng; Zhang, Lei; Han, Jing; Lu, Yang; Tang, Fan; Li, Yabin; Chang, Jian-Feng; Sun, Feng; Yang, Xiaomei; Sun, Fang-Lin; Chen, Su

doi:10.1038/s41418-019-0450-2

Cited by 36 publications

(26 citation statements)

References 43 publications

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“…This metabolic plasticity is common in cancer cells, as it allows them to switch between oxidative phosphorylation (OXPHOS) and glycolysis in response to their environment ( 18 ). To remove the cell’s ability to switch on OXPHOS, we pre-treated the NSCLC cells with oligomycin A, a specific inhibitor of mitochondrial ATP synthase ( 19 ). We found that, although intracellular ATP levels remained high in hypoxic cells, oligomycin A significantly reduced intracellular ATP levels following the addition of HBO ( Figure 1F ).…”

Section: Resultsmentioning

confidence: 99%

Hyperbaric Oxygen Therapy Represses the Warburg Effect and Epithelial–Mesenchymal Transition in Hypoxic NSCLC Cells via the HIF-1α/PFKP Axis

Zhang

Min

et al. 2021

Front. Oncol.

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BackgroundTumor cells initiate hypoxia-induced mechanisms to fuel cell proliferation, invasion, and metastasis, largely mediated by low O2-responsive Hypoxia-Inducible Factor 1 Alpha (HIF-1α). Therefore, hyperbaric oxygen therapy (HBO) is now being studied in cancer patients, but its impact upon non-small-cell lung cancer (NSCLC) cell metabolism remains uncharacterized.MethodsWe employed the NSCLC cell lines A549 and H1299 for in vitro studies. Glucose uptake, pyruvate, lactate, and adenosine triphosphate (ATP) assays were used to assess aerobic glycolysis (Warburg effect). A quantitative glycolytic flux model was used to analyze the flux contributions of HIF-1α-induced glucose metabolism genes. We used a Lewis lung carcinoma (LLC) murine model to measure lung tumorigenesis in C57BL/6J mice.ResultsHBO suppressed hypoxia-induced HIF-1α expression and downstream HIF-1α signaling in NSCLC cells. One HIF-1α-induced glucose metabolism gene—Phosphofructokinase, Platelet (PFKP)—most profoundly enhanced glycolytic flux under both low- and high-glucose conditions. HBO suppressed hypoxia-induced PFKP transactivation and gene expression via HIF-1α downregulation. HBO’s suppression of the Warburg effect, suppression of hyperproliferation, and suppression of epithelial-to-mesenchymal transition (EMT) in hypoxic NSCLC cell lines is mediated by the HIF-1α/PFKP axis. In vivo, HBO therapy inhibited murine LLC lung tumor growth in a Pfkp-dependent manner.ConclusionsHBO’s repression of the Warburg effect, repression of hyperproliferation, and repression of EMT in hypoxic NSCLC cells is dependent upon HIF-1α downregulation. HIF-1α’s target gene PFKP functions as a central mediator of HBO’s effects in hypoxic NSCLC cells and may represent a metabolic vulnerability in NSCLC tumors.

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Section: Resultsmentioning

confidence: 99%

Hyperbaric Oxygen Therapy Represses the Warburg Effect and Epithelial–Mesenchymal Transition in Hypoxic NSCLC Cells via the HIF-1α/PFKP Axis

Zhang

Min

et al. 2021

Front. Oncol.

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“…This major step describes the transformation of BL21 cells with the pET42b (+) plasmid encoding the H2B protein (GST-H2B) and purification of this protein. Please also refer to ( Jing et al., 2020 ) for an example of this step. Take the competent BL21 cells from the −80°C freezer and thaw the cells on ice.…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

In vitro ubiquitination and degradation of bacteria-purified human histone H2B by the nucleoli fractions

Zhang

Liu

et al. 2021

STAR Protocols

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Summary Histones are the main components of chromatin, and the protein levels of histones significantly affect chromatin assembly. Here, we describe detailed protocols for histone H2B purification from bacteria and for the separation of nucleolar fractions and cytoplasmic and nucleoplasmic fractions. Finally, the in vitro ubiquitination and degradation of H2B by distinct cellular fractions are described. For complete details on the use and execution of this protocol, please refer to Liu et al. (2021) .

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“…Monoubiquitination of histone H2B on lysine 120 (H2Bub1) is an epigenetic mark generally associated with transcriptional activation, and H2Bub1 negatively regulates the Warburg effect and tumorigenesis likely through controlling the expression of multiple mitochondrial respiratory genes, which are essential for OXPHOS (oxidative phosphorylation), through interacting with pyruvate kinase M2 (PKM2), the rate-limiting enzyme of glycolysis [137]. Interestingly, H2Bub1 regulates the expression of SLC7A11 and a group of ionbinding genes that function in multiple metabolismrelated processes, indicating that H2Bub1 is a novel epigenetic regulator of ferroptosis.…”

Section: Lymphocyte-specific Helicase (Lsh) Acts As An Epigenetic Regmentioning

confidence: 99%

The epigenetic regulators and metabolic changes in ferroptosis-associated cancer progression

et al. 2020

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Ferroptosis, a novel form of regulated cell death, is different from other types of cell death in morphology, genetics and biochemistry. Increasing evidence indicates that ferroptosis has significant implications on cell death linked to cardiomyopathy, tumorigenesis, and cerebral hemorrhage to name a few. Here we summarize current literature on ferroptosis, including organelle dysfunction, signaling transduction pathways, metabolic reprogramming and epigenetic regulators in cancer progression. With regard to organelles, mitochondria-induced cysteine starvation, endoplasmic reticulum-related oxidative stress, lysosome dysfunction and golgi stress-related lipid peroxidation all contribute to induction of ferroptosis. Understanding the underlying mechanism in ferroptosis could provide insight into the treatment of various intractable diseases including cancers.

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Epigenetic regulation of the Warburg effect by H2B monoubiquitination

Cited by 36 publications

References 43 publications

Hyperbaric Oxygen Therapy Represses the Warburg Effect and Epithelial–Mesenchymal Transition in Hypoxic NSCLC Cells via the HIF-1α/PFKP Axis

Hyperbaric Oxygen Therapy Represses the Warburg Effect and Epithelial–Mesenchymal Transition in Hypoxic NSCLC Cells via the HIF-1α/PFKP Axis

In vitro ubiquitination and degradation of bacteria-purified human histone H2B by the nucleoli fractions

The epigenetic regulators and metabolic changes in ferroptosis-associated cancer progression

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