Site-specific prediction of O-GlcNAc modification in proteins using evolutionary scale model DOI Creative Commons
Ayesha Khalid, Afshan Kaleem, Wajahat M. Qazi

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(12), P. e0316215 - e0316215

Published: Dec. 31, 2024

Protein glycosylation, a vital post-translational modification, is pivotal in various biological processes and disease pathogenesis. Computational approaches, including protein language models machine learning algorithms, have emerged as valuable tools for predicting O- GlcNAc sites, reducing experimental costs, enhancing efficiency. However, the literature has not reported prediction of O -GlcNAc sites through evolutionary scale model (ESM). Therefore, this study employed ESM-2 site humans. Approximately 1100 - linked glycoprotein sequences retrieved from database were utilized training. The exhibited consistent improvement over epochs, achieving an accuracy 78.30%, recall precision 61.31%, F1-score 68.74%. compared to traditional which show overfitting on same data up 99%, outperforms terms optimal training testing predictions. These findings underscore effectiveness accurately within human proteins. Accurately proteins can significantly advance glycoproteomic research by our understanding function mechanisms, aiding developing targeted therapies, facilitating biomarker discovery improved diagnosis treatment. Furthermore, future studies should focus more diverse types, longer sequence lengths, higher computational resources evaluate parameters. Accurate might enhance investigation site-specific functions physiology diseases.

Language: Английский

Unbiasedly decoding the tumor microenvironment with single-cell multiomics analysis in pancreatic cancer DOI Creative Commons
Yifan Fu, Jinxin Tao, Tao Liu

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: July 9, 2024

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with poor prognosis and limited therapeutic options. Research on the tumor microenvironment (TME) of PDAC has propelled development immunotherapeutic targeted strategies promising future. The emergence single-cell sequencing mass spectrometry technologies, coupled spatial omics, collectively revealed heterogeneity TME from multiomics perspective, outlined trajectories cell lineages, important functions previously underrated myeloid cells stroma cells. Concurrently, these findings necessitated more refined annotations biological at cluster or level. Precise identification all clusters urgently needed to determine whether they have been investigated adequately identify target antitumor potential, design compatible treatment strategies, resistance. Here, we summarize recent research level, an unbiased focus potential classification bases every cellular component within TME, look forward prospects integrating data retrospectively reusing bulk data, hoping provide new insights into TME.

Language: Английский

Citations

5
Biological functions of 5-methylcytosine RNA-binding proteins and their potential mechanisms in human cancers DOI Creative Commons
Tingting Zhao, Zhe Zhang, Zhuo Chen

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 7, 2025

The 5-methylcytosine (m5C) modification is a crucial epigenetic RNA modification, which involved in the post-transcriptional regulation of genes. It plays an important role various biological processes, including cell metabolism, growth, apoptosis, and tumorigenesis. By affecting proliferation, migration, invasion, drug sensitivity tumor cells, m5C methylation vital part initiation progression tumors closely associated with poor prognosis. m5C-related proteins are categorized into three functional groups: methyltransferases (m5C writers), demethylases erasers), methyl-binding readers). This paper introduces several common methodologies for detecting methylation; reviews molecular structure functions readers, ALYREF, YBX1, YBX2, RAD52, YTHDF2, FMRP, SRSF2. further summarizes their roles regulatory mechanisms tumors, offering novel targets insights treatment.

Language: Английский

Citations

0
Cell-free DNA: plays an essential role in early diagnosis and immunotherapy of pancreatic cancer DOI Creative Commons
Yi Wen, Grace Zhao, Chunhua Dai

et al.

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

Published: March 7, 2025

Pancreatic cancer is renowned for its aggressive nature and dismal prognosis, with the majority of patients diagnosed at an advanced stage. The prognosis pancreatic can be improved by early diagnosis effective treatment. Circulating cell-free DNA (cfDNA) has emerged as a promising biomarker monitoring cancer. This research presents review circulating essential role in immunotherapy detection methods cfDNA, potential diagnostic biomarker, latest progress cfDNA-based are discussed. findings suggest that cfDNA plays vital personalised treatment cancer, holding great promise improving patient outcomes.

Language: Английский

Citations

0
Targeting cTRIP12 counteracts ferroptosis resistance and augments sensitivity to immunotherapy in pancreatic cancer DOI Creative Commons

Hongyi Lin,

Shuncang Zhu,

Yinghao Chen

et al.

Drug Resistance Updates, Journal Year: 2025, Volume and Issue: unknown, P. 101240 - 101240

Published: March 1, 2025

Current therapeutic strategies for pancreatic ductal adenocarcinoma (PDAC) have limited efficacy in increasing patient survival rates, largely due to ferroptosis resistance and immunosuppression. The aim of this study is identify molecular mechanisms associated with immunosuppression PDAC tumour cells. Circular RNA sequencing (circRNA-seq) was performed on clinical samples potential circRNAs that mediate resistance. C11-BODIPY staining, FerroOrange the glutathione ratio, malondialdehyde quantification, transmission electron microscopy were employed assess ferroptosis. pulldown, mass spectrometry, immunoprecipitation, coimmunoprecipitation assays conducted investigate involved. A HuNSG mouse xenograft model utilized validate agents. circRNA derived from TRIP12 (cTRIP12) identified resistant cTRIP12 knockdown increased sensitivity cells immunotherapy. Subsequent mechanistic studies revealed specifically binds O-linked N-acetylglucosamine transferase (OGT) protein increases intracellular O-GlcNAcylation levels, leading levels ferritin heavy chain (FTH) PD-L1 Notably, high expression suppressed immune by functioning as a scaffold through its interaction OGT kinase R-like endoplasmic reticulum (PERK). inhibition induced reducing FTH synergistically immunotherapy efficacy. In vivo animal experiments confirmed triple therapy consisting GSK2656157, erastin, anti-CTLA-4 effectively progression tumours expression. We elucidated underlying simultaneous occurrence suppression patients. Our provides novel strategy could promote increase

Language: Английский

Citations

0
The impact of metabolic reprogramming on tertiary lymphoid structure formation: enhancing cancer immunotherapy DOI Creative Commons

Meng-Jie Zhang,

Yan Wen, Zhi‐Jun Sun

et al.

BMC Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 13, 2025

Cancer immunotherapy has achieved unprecedented success in the field of cancer therapy. However, its potential is constrained by a low therapeutic response rate. Tertiary lymphoid structure (TLS) plays crucial role antitumor immunity and associated with good prognosis. Metabolic reprogramming, as hallmark tumor microenvironment, can influence promote formation follicular helper T cells germinal centers. many current studies focus on correlation between metabolism TLS factors, there insufficient direct evidence to suggest that drives formation. This review provided comprehensive summary relationship formation, highlighting glucose metabolism, lipid amino acid vitamin metabolism. In future, an in-depth exploration how affects cell interactions microorganisms will significantly advance our understanding metabolism-enhanced immunity.

Language: Английский

Citations

0
Targeting PGM3 abolishes SREBP-1 activation-hexosamine synthesis feedback regulation to effectively suppress brain tumor growth DOI Creative Commons

Huali Su,

Yubin Zhong,

Liqing He

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(16)

Published: April 18, 2025

Elevated hexosamine biosynthesis fuels tumor growth by facilitating protein and lipid glycosylation. But which enzyme in this pathway is better to serve as an antitumor target remains unclear. Here, we revealed that targeting GFAT1, the rate-limiting synthesis, exhibits limited inhibitory effects on glioblastoma (GBM), most lethal brain tumor. This outcome due compensation of NAGK-mediated salvage pathway. Unexpectedly, inhibiting PGM3, controls flux both de novo synthesis pathways, down-regulates expression other enzymes suppresses SREBP-1, a critical lipogenic transcription factor, effectively GBM growth. SREBP-1 transcriptionally up-regulates enzymes, while inhibition these turn activation via reducing N-glycosylation its transporter, SCAP. Our study identified PGM3 promising for treating GBM. Its disrupts activation-hexosamine positive feedback regulation eliminate cells.

Language: Английский

Citations

0
Review article: the role of epigenetics as an underlying regulator of the immune responses in Parkinson’s disease DOI Creative Commons

Maria Georgoula,

Panagiotis Ntavaroukas,

Barry J. Campbell

et al.

Epigenetics Reports, Journal Year: 2024, Volume and Issue: 2(1), P. 1 - 14

Published: Sept. 10, 2024

Language: Английский

Citations

0
GFPT2: A novel biomarker in mesothelioma for diagnosis and prognosis and its molecular mechanism in malignant progression DOI
Wei Jia, Suiqing Zhou, Gang Chen

et al.

British Journal of Cancer, Journal Year: 2024, Volume and Issue: 131(9), P. 1529 - 1542

Published: Sept. 24, 2024

Language: Английский

Citations

0
O-GlcNAcylation in ovarian tumorigenesis and its therapeutic implications DOI
Lu Xia, Jie Mei, Min Huang

et al.

Translational Oncology, Journal Year: 2024, Volume and Issue: 51, P. 102220 - 102220

Published: Nov. 30, 2024

Language: Английский

Citations

0
Site-specific prediction of O-GlcNAc modification in proteins using evolutionary scale model DOI Creative Commons
Ayesha Khalid, Afshan Kaleem, Wajahat M. Qazi

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(12), P. e0316215 - e0316215

Published: Dec. 31, 2024

Protein glycosylation, a vital post-translational modification, is pivotal in various biological processes and disease pathogenesis. Computational approaches, including protein language models machine learning algorithms, have emerged as valuable tools for predicting O- GlcNAc sites, reducing experimental costs, enhancing efficiency. However, the literature has not reported prediction of O -GlcNAc sites through evolutionary scale model (ESM). Therefore, this study employed ESM-2 site humans. Approximately 1100 - linked glycoprotein sequences retrieved from database were utilized training. The exhibited consistent improvement over epochs, achieving an accuracy 78.30%, recall precision 61.31%, F1-score 68.74%. compared to traditional which show overfitting on same data up 99%, outperforms terms optimal training testing predictions. These findings underscore effectiveness accurately within human proteins. Accurately proteins can significantly advance glycoproteomic research by our understanding function mechanisms, aiding developing targeted therapies, facilitating biomarker discovery improved diagnosis treatment. Furthermore, future studies should focus more diverse types, longer sequence lengths, higher computational resources evaluate parameters. Accurate might enhance investigation site-specific functions physiology diseases.

Language: Английский

Citations

0