WTAP promotes macrophage recruitment and increases VEGF secretion via N6-methyladenosine modification in corneal neovascularization

Bai, Yanhui; Jiao, Xiaohang; Hu, Jinge; Xue, Wenxin; Zhou, Ziyu; Wang, Weiqun

doi:10.1016/j.bbadis.2023.166708

Cited by 10 publications

(2 citation statements)

References 48 publications

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“…However, in cells with METTL14 knockdown used for a psoriasis study, the m6A level of HIF-1α mRNA decreased, but the protein expression increased[ 36 ]. m6A modification directly affected the translation efficiency of HIF-1α instead of the mRNA level[ 37 ]. Therefore, the relation of m6A modification and HIF-1α remains controversial.…”

Section: Discussionmentioning

confidence: 99%

N6-methyladenosine modification of hypoxia-inducible factor-1α regulates Helicobacter pylori-associated gastric cancer via the PI3K/AKT pathway

An,

Hu,

et al. 2024

World J Gastrointest Oncol

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BACKGROUND Helicobacter pylori (H. pylori ) colonizes the human gastric mucosa and is implicated in the development of gastric cancer (GC). The tumor microenvironment is characterized by hypoxia, where hypoxia-inducible factor-1α (HIF-1α) plays a key role as a transcription factor, but the mechanisms underlying H. pylori -induced HIF-1α expression and carcinogenesis remain unclear. AIM To explore the underlying mechanism of H. pylori -induced HIF-1α expression in promoting the malignant biological behavior of gastric epithelial cells (GES-1). METHODS The study was conducted with human GES-1 cells in vitro . Relative protein levels of methyltransferase-like protein 14 (METTL14), HIF-1α, main proteins of the PI3K/AKT pathway, epithelial-mesenchymal transition (EMT) biomarkers, and invasion indicators were detected by Western blot. Relative mRNA levels of METTL14 and HIF-1α were detected by quantitative reverse transcription-polymerase chain reaction. mRNA stability was evaluated using actinomycin D, and the interaction between METTL14 and HIF-1α was confirmed by immunofluorescence staining. Cell proliferation and migration were evaluated by cell counting kit-8 assay and wound healing assay, respectively. RESULTS H. pylori promoted HIF-1α expression and activated the PI3K/AKT pathway. Notably, METTL14 was downregulated in H. pylori -infected gastric mucosal epithelial cells and positively regulated HIF-1α expression. Functional experiments showed that the overexpression of HIF-1α or knockdown of METTL14 enhanced the activity of the PI3K/AKT pathway, thereby driving a series of malignant transformation, such as EMT and cell proliferation, migration, and invasion. By contrast, the knockdown of HIF-1α or overexpression of METTL14 had an opposite effect. CONCLUSION H. pylori- induced underexpression of METTL14 promotes the translation of HIF-1α and accelerates tumor progression by activating the PI3K/AKT pathway. These results provide novel insights into the carcinogenesis of GC.

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Section: Discussionmentioning

confidence: 99%

N6-methyladenosine modification of hypoxia-inducible factor-1α regulates Helicobacter pylori-associated gastric cancer via the PI3K/AKT pathway

An,

Hu,

et al. 2024

World J Gastrointest Oncol

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“…METTL3, WTAP, YTHDF1, and IGF2BP1 also regulated innate immune cells in the microenvironments of colorectal cancer [93], corneal neovascularization [94], gastric cancer [95], and HCC [96], reinforcing the roles of m6A in immune cell infiltration.…”

Section: M6a and The Immune Microenvironmentmentioning

confidence: 99%

N6-Methyladenosine (m6A) Modification in Natural Immune Cell-Mediated Inflammatory Diseases

Teng,

Yi,

Chen

et al. 2023

J Innate Immun

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The post-transcriptional N6-methyladenosine (m6A) modification of RNA influences stability, transport, and translation with implications for various physiological and pathological processes. Immune cell development, differentiation, and activation are also thought to be regulated by m6A and affect host defense against pathogens and inflammatory response with impacts on infectious, neoplastic, autoimmune, cardiovascular, hepatic, and osteal diseases. The current review summarizes recent research on m6A in monocyte/macrophages, neutrophils, dendritic cells, natural killer cells, and microglia and gives insights into epigenetic modifications of the immune system and novel therapeutic strategies for immune-related diseases.

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WTAP promotes the progression of ulcerative colitis by silencing the expression of CES2 through m6A modification

Xie,

Cheng,

Chen

et al. 2024

Journal of Autoimmunity

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WTAP promotes macrophage recruitment and increases VEGF secretion via N6-methyladenosine modification in corneal neovascularization

Cited by 10 publications

References 48 publications

N6-methyladenosine modification of hypoxia-inducible factor-1α regulates Helicobacter pylori-associated gastric cancer via the PI3K/AKT pathway

N6-methyladenosine modification of hypoxia-inducible factor-1α regulates Helicobacter pylori-associated gastric cancer via the PI3K/AKT pathway

N6-Methyladenosine (m6A) Modification in Natural Immune Cell-Mediated Inflammatory Diseases

WTAP promotes the progression of ulcerative colitis by silencing the expression of CES2 through m6A modification

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