METTL3 mediated WISP1 m6A modification promotes epithelial-mesenchymal transition and tumorigenesis in laryngeal squamous cell carcinoma via m6A reader IGF2BP1

Gene, Journal Year: 2025, Volume and Issue: 941, P. 149222 - 149222

Published: Jan. 5, 2025

Language: Английский

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The role and mechanism of m6A methylation in diabetic nephropathy

Life Sciences, Journal Year: 2025, Volume and Issue: 363, P. 123355 - 123355

Published: Jan. 6, 2025

Language: Английский

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METTL3 Potentiates M2 Macrophage‐Driven MMT to Aggravate Renal Allograft Fibrosis via the TGF‐β1/Smad3 Pathway

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Abstract METTL3, a key enzyme in N6‐methyladenosine (m6A) modification, plays crucial role the progression of renal fibrosis, particularly chronic active allograft rejection (CAR). This study explored mechanisms by which METTL3 promotes focusing on its macrophage‐to‐myofibroblast transition (MMT). Using comprehensive experimental approach, including TGF‐β1‐induced MMT cell models, conditional knockout (METTL3 KO) mice, and biopsy samples from patients with CAR, investigates involvement METTL3/Smad3 axis driving fibrosis during episodes CAR. We found that elevated m6A modification levels strongly correlated enhanced increased fibrotic severity. significantly Smad3, decreased Smad3 expression, inhibited M2‐driven MMT. knockdown siRNA (siSmad3) further MMT, while overexpression rescued inhibitory effects silencing, restoring tissue damage. Additionally, inhibitor STM2457 effectively reversed alleviated damage These findings highlight enhances CAR promoting TGF‐β1/Smad3 axis, suggesting is promising therapeutic target for mitigating

Language: Английский

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An overview of CCN4 (WISP1) role in human diseases

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 27, 2024

Abstract CCN4 (cellular communication network factor 4), a highly conserved, secreted cysteine-rich matricellular protein is emerging as key player in the development and progression of numerous disease pathologies, including cancer, fibrosis, metabolic inflammatory disorders. Over past two decades, extensive research on its family members uncovered their diverse cellular mechanisms biological functions, but not limited to cell proliferation, migration, invasion, angiogenesis, wound healing, repair, apoptosis. Recent studies have demonstrated that aberrant expression and/or associated downstream signaling vast array pathophysiological etiology, suggesting could be utilized only non-invasive diagnostic or prognostic marker, also promising therapeutic target. The cognate receptor remains elusive till date, which limits understanding mechanistic insights driven pathologies. However, agents directed against begin make way into clinic, may start change. Also, significance underexplored, hence further needed shed more light tissue specific functions better understand clinical translational benefit. This review highlights compelling evidence overlapping functional regulated by CCN4, addition addressing challenges, study limitations knowledge gaps biology potential.

Language: Английский

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Methyltransferase-like 3 is a target for the diagnose and therapy of clear cell renal carcinoma

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 17, 2025

Patients diagnosed with clear cell renal carcinoma (ccRCC) frequently exhibit metastatic disease, which complicates treatment strategies, underscoring the urgent need for mechanistic insights and early diagnostic biomarkers. Current research is dedicated to uncovering mechanisms behind ccRCC development resistance treatment, a particular focus on role of methyltransferase-like 3 (METTL3) in RNA N 6 -methyladenosine modification, key gene regulatory process. This review synthesizes current evidence METTL3’s functions, revealing its oncogenic activity through m A-mediated regulation stability translation, promotes tumor progression, metastasis, chemoresistance. We further explore dual therapeutic relevance, including utility as prognostic biomarker targeting via novel strategies such small-molecule inhibitors (e.g., Erianin ) combination therapies mTOR or immune checkpoint inhibitors. By consolidating these advances, this positions METTL3 critical node advancing precision medicine ccRCC.

Language: Английский

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N6-methyladenosine triggers renal fibrosis via enhancing translation and stability of ZEB2 mRNA

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(9), P. 107598 - 107598

Published: July 24, 2024

Language: Английский

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N6-methyladenine RNA methylation epigenetic modification and diabetic microvascular complications

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 4, 2024

N6-methyladensine (m

Language: Английский

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Unleashing the pathological role of epithelial-to-mesenchymal transition in diabetic nephropathy: The intricate connection with multifaceted mechanism

World Journal of Nephrology, Journal Year: 2024, Volume and Issue: 13(2)

Published: June 25, 2024

Renal epithelial-to-mesenchymal transition (EMT) is a process in which epithelial cells undergo biochemical changes and transform into mesenchymal-like cells, resulting renal abnormalities, including fibrosis. EMT can cause diabetic nephropathy through triggering kidney fibrosis, inflammation, functional impairment. The diverse molecular pathways that drive EMT-mediated fibrosis are not utterly known. Targeting key signaling involved may help ameliorate improve function. In such settings, understanding precisely the complicated networks critical for developing customized therapies to intervene nephropathy.

Language: Английский

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METTL3-mediated m6A modification of EGR1 mRNA promotes T2DM vasculopathy

Cellular Signalling, Journal Year: 2024, Volume and Issue: 127, P. 111564 - 111564

Published: Dec. 13, 2024

Language: Английский

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