METTL3 attenuates proliferative vitreoretinopathy and epithelial‐mesenchymal transition of retinal pigment epithelial cells via wnt/β‐catenin pathway

Ma, Xinqi; Long, Chongde; Wang, Fangyu; Lou, Bingsheng; Yuan, Miner; Duan, Fang; Yang, Yao; Li, Jiaqing; Qian, Xiaobing; Zeng, Junfeng; Lin, Shuibin; Shen, Huangxuan; Lin, Xiaofeng

doi:10.1111/jcmm.16476

Cited by 45 publications

(30 citation statements)

References 38 publications

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“…Similarly, Dickkopf‐1 (DKK1) can reduce the osteogenic potential of BMSCs and cause bone loss 31,32 . Previous studies have shown that Mettl3 could regulate the Wnt/β‐catenin pathway 33,34 . However, the regulatory mechanism of Mettl3 influences the bone differentiation of OP‐BMSCs through the canonical Wnt pathway is unknown.…”

Section: Introductionmentioning

confidence: 99%

METTL3‐m⁶A methylase regulates the osteogenic potential of bone marrow mesenchymal stem cells in osteoporotic rats via the Wnt signalling pathway

Tang

Yang

et al. 2022

Cell Proliferation

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Objectives Bone marrow mesenchymal stem cells (BMSCs) hold a high osteogenic differentiation potential, but the mechanisms that control the osteogenic ability of BMSCs from osteoporosis (OP‐BMSCs) need further research. The purpose of this experiment is to discuss the osteogenic effect of Mettl3 on OP‐BMSCs and explore new therapeutic target that can enhance the bone formation ability of OP‐BMSCs. Materials and Methods The bilateral ovariectomy (OVX) method was used to establish the SD rat OP model. Dot blots were used to reveal the different methylation levels of BMSCs and OP‐BMSCs. Lentiviral‐mediated overexpression of Mettl3 was applied in OP‐BMSCs. QPCR and WB detected the molecular changes of osteogenic‐related factors and Wnt signalling pathway in vitro experiment. The staining of calcium nodules and alkaline phosphatase detected the osteogenic ability of OP‐BMSCs. Micro‐CT and histological examination evaluated the osteogenesis of Mettl3 in OP rats in vivo. Results The OP rat model was successfully established by OVX. Methylation levels and osteogenic potential of OP‐BMSCs were decreased in OP‐BMSCs. In vitro experiment, overexpression of Mettl3 could upregulate the osteogenic‐related factors and activate the Wnt signalling pathway in OP‐BMSCs. However, osteogenesis of OP‐BMSCs was weakened by treatment with the canonical Wnt inhibitor Dickkopf‐1. Micro‐CT showed that the Mettl3(+) group had an increased amount of new bone formation at 8 weeks. Moreover, the results of histological staining were the same as the micro‐CT results. Conclusions Taken together, the methylation levels and osteogenic potential of OP‐BMSCs were decreased in OP‐BMSCs. In vitro and in vivo studies, overexpression of Mettl3 could partially rescue the decreased bone formation ability of OP‐BMSCs by the canonical Wnt signalling pathway. Therefore, Mettl3 may be a key targeted gene for bone generation and therapy of bone defects in OP patients.

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Section: Introductionmentioning

confidence: 99%

METTL3‐m⁶A methylase regulates the osteogenic potential of bone marrow mesenchymal stem cells in osteoporotic rats via the Wnt signalling pathway

Tang

Yang

et al. 2022

Cell Proliferation

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“…To further investigate the possible mechanism of MTDH regulating EMT, given that m6A RNA methylation is crucial for promoting EMT in cancer ( Chen et al., 2020 ; Jin et al., 2020 ; Lin et al., 2019 ; Ma et al., 2021 ; Xu et al., 2021 ), the correlation between m6A RNA methylation and MTDH was performed. As shown in Figures 6 A–6H, the estimated score of m6A RNA methylation was significantly correlated with MTDH expression in BLCA (R = 0.6, p < 0.01), BRCA (R = 0.54, p < 0.01), CHOL (R = 0.73, p < 0.01), LUAD (R = 0.43, p < 0.01), HNSC (R = 0.53, p < 0.01), KIRC (R = 0.5, p < 0.01), KIRP (R = 0.64, p < 0.01), and LIHC (R = 0.47, p < 0.01).…”

Section: Resultsmentioning

confidence: 99%

“…m6A RNA methylation is crucial for the regulation of EMT through WNT/beta-catenin, PI3K/Akt, LAST2/YAP pathway, or Sox4 mRNA stability ( Chen et al., 2020 ; Jin et al., 2020 ; Lin et al., 2019 ; Ma et al., 2021 ; Xu et al., 2021 ). Our study showed that the most differential genes in the high expression of MTDH tumor might be enriched in the activation of the PI3K/Akt pathway, indicating MTDH may regulate PI3K/Akt-induced EMT by m6A RNA methylation.…”

Section: Discussionmentioning

confidence: 99%

MTDH associates with m6A RNA methylation and predicts cancer response for immune checkpoint treatment

et al. 2021

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Summary Immune checkpoint blockade (ICB) persistently provides a prognosis improvement but only in a small fraction of patients with cancer due to immunotherapy resistance induced by the consecutive activated oncogenic pathways, including MAPK, Akt, and WNT pathway partially driven by Metadherin (MTDH). However, there is no study to investigate the potential role and mechanisms of MTDH in ICB-treated cancers. Here, we systematically explored the cohorts from The Cancer Genome Atlas (TCGA) and independent cancer cohorts. Elevated MTDH expression was founded to associate with a worse overall survival and poorer immune response in patients with cancer. Dysregulated tumor-infiltrating immune cells and inhibitory immune checkpoint expression were correlated with MTDH expression. Furthermore, the mutual interactions between epithelial-to-mesenchymal-transition, m6A-RNA-methylation, and MTDH may illustrate the potential mechanisms of MTDH resistant to ICB treatment. Although more designed experiments and trials are needed in the future, targeting MTDH may help to overcome immunotherapy resistance in a wide range of cancers.

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“…Multiple agents are being investigated in preclinical in vitro and in vivo studies. Agents that inhibit RPE cell proliferation, migration, and EMT by targeting TGFb or the TGFb-signaling cascade, including Runt-related transcription factor 1 (RUNX1) inhibitors [50 && ], protein kinase A inhibitors [53], Smad signaling inhibitors [45,54], METTL3 overexpression [55], p38 inhibition [46,56], and micro-RNA approaches. Other therapeutic targets being investigated include inhibition of epidermal growth factor [57,58], FGF [59], and rho kinase [60 && ].…”

Section: Novel Targets For Proliferative Vitreoretinopathy Inhibitionmentioning

confidence: 99%

Translational and clinical advancements in management of proliferative vitreoretinopathy

Shahlaee

Woeller

Philp

et al. 2022

Current Opinion in Ophthalmology

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Purpose of reviewDespite advancement in the surgical instrumentation and techniques, proliferative vitreoretinopathy (PVR) remains the most common cause for failure of rhegmatogenous retinal detachment (RRD) repair. This review discusses ongoing translational and clinical advancements in PVR. Recent findingsPVR represents an exaggerated and protracted scarring process that can occur after RRD. The primary cell types involved are retinal pigment epithelium, glial, and inflammatory cells. They interact with growth factors and cytokines derived from the breakdown of the blood--retinal barrier that trigger a cascade of cellular processes, such as epithelial--mesenchymal transition, cell migration, chemotaxis, proliferation, elaboration of basement membrane and collagen and cellular contraction, leading to overt retinal pathology. Although there are currently no medical therapies proven to be effective against PVR in humans, increased understanding of the risks factors and pathophysiology have helped guide investigations for molecular targets of PVR. The leading therapeutic candidates are drugs that mitigate growth factors, inflammation, and proliferation are the leading therapeutic candidates.

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METTL3 attenuates proliferative vitreoretinopathy and epithelial‐mesenchymal transition of retinal pigment epithelial cells via wnt/β‐catenin pathway

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 45 publications

References 38 publications

METTL3‐m⁶A methylase regulates the osteogenic potential of bone marrow mesenchymal stem cells in osteoporotic rats via the Wnt signalling pathway

METTL3‐m⁶A methylase regulates the osteogenic potential of bone marrow mesenchymal stem cells in osteoporotic rats via the Wnt signalling pathway

MTDH associates with m6A RNA methylation and predicts cancer response for immune checkpoint treatment

Translational and clinical advancements in management of proliferative vitreoretinopathy

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METTL3 attenuates proliferative vitreoretinopathy and epithelial‐mesenchymal transition of retinal pigment epithelial cells via wnt/β‐catenin pathway

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 45 publications

References 38 publications

METTL3‐m6A methylase regulates the osteogenic potential of bone marrow mesenchymal stem cells in osteoporotic rats via the Wnt signalling pathway

METTL3‐m6A methylase regulates the osteogenic potential of bone marrow mesenchymal stem cells in osteoporotic rats via the Wnt signalling pathway

MTDH associates with m6A RNA methylation and predicts cancer response for immune checkpoint treatment

Translational and clinical advancements in management of proliferative vitreoretinopathy

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METTL3‐m⁶A methylase regulates the osteogenic potential of bone marrow mesenchymal stem cells in osteoporotic rats via the Wnt signalling pathway

METTL3‐m⁶A methylase regulates the osteogenic potential of bone marrow mesenchymal stem cells in osteoporotic rats via the Wnt signalling pathway