Integration of 101 machine learning algorithm combinations to unveil m6A/m1A/m5C/m7G-associated prognostic signature in colorectal cancer

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 18, 2025

Colorectal cancer (CRC) is the most common malignancy in digestive system, with a lower 5-year overall survival rate. There increasing evidence showing that RNA modification regulators such as m1A, m5C, m6A, and m7G play crucial roles tumor progression. However, prognostic role of integrated m6A/m5C/m1A/m7G methylation modifications CRC has not been reported requires further investigation. Five cohorts 989 samples were first retrieved from The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) databases. Then, Three m6A/m1A/m5C/m7G-associated molecular subtypes identified TCGA cohort via consensus clustering analysis, 1710 co-expression module genes associated obtained weighted gene network analysis (WGCNA) results. After conducting univariate Cox each retaining genes, an methylation-related signature (RMS) was developed through combination 101 algorithms. RMS exhibited strong accuracy robustness predicting outcomes across distinct (TCGA, GSE17536, GSE17537, GSE29612, GSE38832) demonstrated good performance compared previously risk signatures. Additionally, independent factor for TCGA, GSE38832 cohorts. patients then stratified into high low-risk groups based on median score five Compared to high-risk groups, group showed increased immune cell infiltration level more benefit immunotherapy chemotherapy drugs. Moreover, six drugs (KU-0063794, temozolomide, DNMDP, ML162, SJ-172550, ML050) Therapeutics Response Portal (CTRP) (BIBX-1382, lomitapide, ZLN005, PPT, panobinostat) PRSM database patients. By integrating data Cell Line Encyclopedia (CCLE) database, potential therapeutic target named TERT single-cell results indicated highly expressed epithelial cells. Overall, our can accurately predict response, indicating promising application clinical practice. These findings may offer guidance prognosis personalized treatment CRC.

Language: Английский

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WTAP/IGF2BP3 Mediated m6A Modification of SOD2 mRNA Aggravates the Tumourigenesis of Colorectal Cancer

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(1)

Published: Jan. 1, 2025

Wilms tumor 1-associated protein (WTAP) has been validated to be a crucial regulator in the tumorigenesis and advancement of diverse malignancies. This study intended probe impacts WTAP on colorectal cancer (CRC) progression from perspective N6-methyladenosine (m6A) modification. The differential expression patterns clinical CRC samples cultured cell lines were via qRT-PCR western blot. Cell function tests conducted with colony formation, transwell, CCK-8. MeRIP-qPCR was identify WTAP-mediated SOD2 (Superoxide dismutase 2) mRNA modification cells. Animal experiments adopted evaluate vivo. exhibited high pattern along Silencing potently restrained growth virto Mechanically, identified as an m6A target WTAP. elevated its stability IGF2BP3-dependent manner. Meanwhile, overexpression could reverse suppressive effect induced by silencing. Molecular therapy targeting WTAP-SOD2 may offer novel insights perspectives for treatment CRC.

Language: Английский

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The role and mechanism of NAT10‐mediated ac4C modification in tumor development and progression

MedComm, Journal Year: 2024, Volume and Issue: 5(12)

Published: Dec. 1, 2024

Abstract RNA modification has emerged as a crucial area of research in epigenetics, significantly influencing tumor biology by regulating metabolism. N‐acetyltransferase 10 (NAT10)‐mediated N4‐acetylcytidine (ac4C) modification, the sole known acetylation eukaryotic RNA, influences cancer pathogenesis and progression. NAT10 is only writer ac4C catalyzes acetyl transfer on targeted helps to improve stability translational efficiency ac4C‐modified RNA. highly expressed associated with poor prognosis pan‐cancers. Based its molecular mechanism biological functions, central factor tumorigenesis, progression, drug resistance, immune escape. Despite increasing focus ac4C, specific regulatory mechanisms remain elusive. The present review thoroughly analyzes current knowledge NAT10‐mediated cancer, highlighting broad influence gene expression biology. This also summarizes limitations perspectives identify new therapeutic targets advance treatment strategies.

Language: Английский

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Acetyltransferase NAT10 promotes an immunosuppressive microenvironment by modulating CD8+ T cell activity in prostate cancer

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: Dec. 9, 2024

Abstract N-acetyltransferase 10 (NAT10), an enzyme responsible for ac4C acetylation, is implicated in cancer progression, though its specific biological function prostate remains insufficiently understood. This study clarifies NAT10’s role and effects on the tumor immune microenvironment. NAT10 expression clinical relevance were assessed through bioinformatics, RT-qPCR, IHC analyses, comparing tissues with normal controls. The impact of cell proliferation, migration, invasion was investigated via vitro assays—including CCK-8, EdU, wound healing, 3D-Transwell—as well as vivo mouse xenograft models organoid studies. Further, influence infiltration examined using flow cytometry, IHC, co-culture assays, ELISA to elucidate downstream chemokine effects, specifically targeting CD8 + T cells. Findings indicated significant upregulation cells, enhancing their proliferative invasive capacities. Notably, suppresses recruitment cytotoxicity CCL25/CCR9 axis, fostering immunosuppressive microenvironment that exacerbates progression. An modification score also devised based targets, providing a novel predictive tool evaluating forecasting immunotherapy responses patients cancer. underscores pivotal modulating microenvironment, offering insights into desert phenomenon identifying promising therapeutic target improving efficacy.

Language: Английский

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The RNA Revolution in the Central Molecular Biology Dogma Evolution

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12695 - 12695

Published: Nov. 26, 2024

Human genome projects in the 1990s identified about 20,000 protein-coding sequences. We are now RNA revolution, propelled by realization that genes determine phenotype beyond foundational central molecular biology dogma, stating inherited linear pieces of DNA transcribed to RNAs and translated into proteins. Crucially, over 95% genome, initially considered junk between genes, encodes essential, functionally diverse non-protein-coding RNAs, raising gene count at least one order magnitude. Most phenotype-determining changes regulatory areas control can directly or indirectly phenotypes regulating protein function, transferring information within organisms, generating DNA. also exhibit high structural, functional, biomolecular interaction plasticity modified via editing, methylation, glycosylation, other mechanisms, which bestow them with intra- extracellular functions without altering underlying is, therefore, currently primary determinant cellular populational functional diversity, disease-linked structural variations, cell function regulation. As demonstrated RNA-based coronavirus vaccines' success, technology is transforming medicine, agriculture, industry, as did advent recombinant 1980s.

Language: Английский

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