PBRM1 Cooperates with YTHDF2 to Control HIF-1α Protein Translation

Shmakova, Alena; Frost, Mark; Batie, Michael; Kenneth, Niall S.; Rocha, Sónia

doi:10.3390/cells10061425

Cited by 14 publications

(13 citation statements)

References 47 publications

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“…Roles and regulatory mechanisms of m 6 A regulators vary with their subcellular locations and in different diseases. Reportedly, stress induced the translocation of YTHDF2 from cytoplasm to nucleus, and unlike the role of cytoplasmic YTHDF2 in mediating RNA degradation, the endonuclear YTHDF2 promoted the cap-independent mRNA translation of HIF-1α, thus contributing to neovascularization [ 21 , 78 ]. M 6 A regulators may also play opposite roles in different diseases or pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, in lung cancer, the crosstalk between polybromo 1 (PBRM1) and YTHDF2 was required for the effective synthesis of HIF-1 protein. YTHDF2 mediated RNA degradation in the cytoplasm under normal conditions, while it translocated into cell nucleus upon hypoxia to promote the cap-independent translation of HIF-1α mRNAs [ 21 ]. Collectively, these studies imply the critical role of m 6 A modification in hypoxia-induced neovascularization.…”

Section: M 6 a Modifications In Pathological Neova...mentioning

confidence: 99%

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The Role of N6-Methyladenosine Modification in Microvascular Dysfunction

Zhang

Wang

et al. 2022

Cells

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Microvascular dysfunction (MVD) has long plagued the medical field despite improvements in its prevention, diagnosis, and intervention. Microvascular lesions from MVD increase with age and further lead to impaired microcirculation, target organ dysfunction, and a mass of microvascular complications, thus contributing to a heavy medical burden and rising disability rates. An up-to-date understanding of molecular mechanisms underlying MVD will facilitate discoveries of more effective therapeutic strategies. Recent advances in epigenetics have revealed that RNA methylation, an epigenetic modification, has a pivotal role in vascular events. The N6-methylation of adenosine (m6A) modification is the most prevalent internal RNA modification in eukaryotic cells, which regulates vascular transcripts through splicing, degradation, translation, as well as translocation, thus maintaining microvascular homeostasis. Conversely, the disruption of the m6A regulatory network will lead to MVD. Herein, we provide a review discussing how m6A methylation interacts with MVD. We also focus on alterations of the m6A regulatory network under pathological conditions. Finally, we highlight the value of m6A regulators as prognostic biomarkers and novel therapeutic targets, which might be a promising addition to clinical medicine.

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Section: Discussionmentioning

confidence: 99%

Section: M 6 a Modifications In Pathological Neova...mentioning

confidence: 99%

The Role of N6-Methyladenosine Modification in Microvascular Dysfunction

Zhang

Wang

et al. 2022

Cells

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“…HBXIP upregulates HIF‐1α in hepatocellular carcinoma cells by promoting METTL3 overexpression to drive their metabolic reprogramming (Yang, Wang, et al, 2021). PBRM1 and MTHFD2 upregulate HIF‐1α and HIF‐2α, respectively, to promote hypoxia signaling pathways and aerobic glycolysis in tumors (Green et al, 2019; Shmakova et al, 2021). Toll‐like receptor and NF‐κB signaling are common molecules and tumor regulatory signaling pathways in the TME.…”

Section: Factors Regulating Rna M6a Modification In the Tmementioning

confidence: 99%

“…In addition to the factors discussed above, other regulators involved in the regulation of tumor RNA m6A modifications either directly or indirectly include HBXIP, PBRM1, MTHFD2, and TLR4 (Green et al, 2019; Jiang et al, 2020; Shmakova et al, 2021; Yang, Wang, et al, 2021). HBXIP upregulates HIF‐1α in hepatocellular carcinoma cells by promoting METTL3 overexpression to drive their metabolic reprogramming (Yang, Wang, et al, 2021).…”

Section: Factors Regulating Rna M6a Modification In the Tmementioning

confidence: 99%

RNA m6A modifications regulate crosstalk between tumor metabolism and immunity

Gu,

Cao,

Chen

et al. 2023

WIREs RNA

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In recent years, m6A modifications in RNA transcripts have arisen as a hot topic in cancer research. Indeed, a number of independent studies have elaborated that the m6A modification impacts the behavior of tumor cells and tumor‐infiltrating immune cells, altering tumor cell metabolism along with the differentiation and functional activity of immune cells. This review elaborates on the links between RNA m6A modifications, tumor cell metabolism, and immune cell behavior, discussing this topic from the viewpoint of reciprocal regulation through “RNA m6A–tumor cell metabolism–immune cell behavior” and “RNA m6A–immune cell behavior–tumor cell metabolism” axes. In addition, we discuss the various factors affecting RNA m6A modifications in the tumor microenvironment, particularly the effects of hypoxia associated with cancer cell metabolism along with immune cell‐secreted cytokines. Our analysis proposes the conclusion that RNA m6A modifications support widespread interactions between tumor metabolism and tumor immunity. With the current viewpoint that long‐term cancer control must tackle cancer cell malignant behavior while strengthening anti‐tumor immunity, the recognition of RNA m6A modifications as a key factor provides a new direction for the targeted therapy of tumors.This article is categorized under: RNA Processing > RNA Editing and Modification RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications

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“…m6A enrichment sequencing or direct RNA sequencing approaches enable identification and quantification of m6A across the transcriptome. Several m6A transcriptome screens have identified m6A methylation sites on HIF-1α [128][129][130][131][132][133] and m6A modification on HIF-1α has recently been confirmed by RNA ImmunoPrecipitation-PCR analysis [134]. To date only one study has mapped the m6A epitranscriptomic is response to low oxygen [135].…”

Section: Metabolomics and Hypoxia Researchmentioning

confidence: 99%

Systems approaches to understand oxygen sensing: how multi-omics has driven advances in understanding oxygen-based signalling

Batie

Kenneth

Rocha

2022

Biochemical Journal

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Hypoxia is a common denominator in the pathophysiology of a variety of human disease states. Insight into how cells detect, and respond to low oxygen is crucial to understanding the role of hypoxia in disease. Central to the hypoxic response is rapid changes in the expression of genes essential to carry out a wide range of functions to adapt the cell/tissue to decreased oxygen availability. These changes in gene expression are co-ordinated by specialised transcription factors, changes to chromatin architecture and intricate balances between protein synthesis and destruction that together establish changes to the cellular proteome. In this article, we will discuss the advances of our understanding of the cellular oxygen sensing machinery achieved through the application of ‘omics-based experimental approaches.

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PBRM1 Cooperates with YTHDF2 to Control HIF-1α Protein Translation

Cited by 14 publications

References 47 publications

The Role of N6-Methyladenosine Modification in Microvascular Dysfunction

The Role of N6-Methyladenosine Modification in Microvascular Dysfunction

RNA m6A modifications regulate crosstalk between tumor metabolism and immunity

Systems approaches to understand oxygen sensing: how multi-omics has driven advances in understanding oxygen-based signalling

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