Detecting the Tumor Prognostic Factors From the YTH Domain Family Through Integrative Pan-Cancer Analysis DOI Creative Commons

Chong-ying Zhu,

Qiwei Yang,

Xin-yue Mu

et al.

Cancer Informatics, Journal Year: 2024, Volume and Issue: 23

Published: Jan. 1, 2024

Objectives: Emerging evidence suggests that N6-methyladenosine (m 6 A) methylation plays a critical role in cancers through various mechanisms. This work aims to reveal the essential of m A “readers” regulation cancer prognosis at pan-cancer level. Methods: Herein, we focused on one special protein family methylation, YT521-B homology (YTH) domain genes, which were observed be frequently dysregulated tumor tissues and closely associated with prognosis. Then, comprehensive analysis modulation was conducted by integrating RNA sequencing (RNAseq) datasets YTH genes clinical information Results: significantly differentially expressed most cancers, particularly increased Gastrointestinal decreased Endocrine Urologic cancers. In addition, they overall survival (OS) disease-specific (DSS) extent, especially lower grade glioma (LGG), thyroid (THCA), liver hepatocellular carcinoma (LIHC) kidney clear cell (KIRC), so some “writers” (METLL3, METLL14, WTAP) “erasers” (FTO, ALKBH5). Further illustrated specifically YTHScore constructed combining 5 as well RWEScore calculated from “readers”-“writers”-“erasers” could dramatically distinguish 4 representative As expected, presented an equally comparable prognostic classification RWEScore. Finally, immune signatures characteristics implied that, activity innate immune, diagnostic age, stage, Tumor-Node-Metastasis (TNM) stage types, might play specific roles modulating Conclusions: The study demonstrated had potential predict prognosis, equal ability compared RWEScore, thus providing insights into biomarkers therapeutic targets

Language: Английский

Epigenetics-targeted drugs: current paradigms and future challenges DOI Creative Commons

Wanlin Dai,

Xinbo Qiao, Yuanyuan Fang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Nov. 26, 2024

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone RNA remodeling, and non-coding regulation. These mechanisms their associated enzymes convey genetic information independently of base sequences, playing essential roles in organismal development homeostasis. Conversely, disruptions epigenetic landscapes critically influence the pathogenesis various human diseases. This understanding has laid robust theoretical groundwork for developing drugs that target epigenetics-modifying pathological conditions. Over past two decades, growing array small molecule targeting such as methyltransferase, deacetylase, isocitrate dehydrogenase, enhancer zeste homolog 2, have been thoroughly investigated implemented therapeutic options, particularly oncology. Additionally, numerous epigenetics-targeted are undergoing clinical trials, offering promising prospects benefits. review delineates epigenetics physiological contexts underscores pioneering studies on discovery implementation drugs. include inhibitors, agonists, degraders, multitarget agents, aiming to identify practical challenges avenues future research. Ultimately, this aims deepen epigenetics-oriented strategies further application settings.

Language: Английский

Citations

24
Writers, readers, and erasers RNA modifications and drug resistance in cancer DOI Creative Commons
Di Chen, Xinyu Gu,

Yeltai Nurzat

et al.

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

Published: Aug. 30, 2024

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.

Language: Английский

Citations

16
Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy DOI Creative Commons
Kiavash Hushmandi, Behzad Einollahi, Seyed Hassan Saadat

et al.

Molecular Metabolism, Journal Year: 2024, Volume and Issue: 84, P. 101952 - 101952

Published: May 3, 2024

Solute carrier (SLC), a diverse family of membrane proteins, are instrumental in orchestrating the intake and efflux nutrients including amino acids, vitamins, ions, nutrients, etc, across cell membranes. This dynamic process is critical for sustaining metabolic demands cancer cells, promoting their survival, proliferation, adaptation to tumor microenvironment. Amino acids fundamental building blocks playing essential roles not only protein synthesis but also nutrient sensing, signaling pathways that can promote tumorigenesis. As key transporters SLCs have emerged as crucial players maintaining cellular acid homeostasis, dysregulation implicated various types. Thus, understanding intricate connections between SLCs, pivotal unraveling novel therapeutic targets strategies. uptake by positively affects progression. However, some studies revealed suppressor function SLCs. Although body evaluated SLC7A11 SLC1A5, SLC proteins studied sufficiently cancer. In this review, we delve into significant impact carriers on growth progression explore current state knowledge field, shedding light molecular mechanisms underlie these relationships highlighting potential avenues future research clinical interventions. comprehensive review provides insights rapidly evolving area biology focusing one most important materials cells need, within superfamily.

Language: Английский

Citations

11
Interplay of m6A RNA methylation and gut microbiota in modulating gut injury DOI Creative Commons
Haixia Wang, Juanjuan Han, Xinan Zhang

et al.

Gut Microbes, Journal Year: 2025, Volume and Issue: 17(1)

Published: Feb. 17, 2025

The gut microbiota undergoes continuous variations among individuals and across their lifespan, shaped by diverse factors encompassing diet, age, lifestyle choices, medication intake, disease states. These microbial inhabitants play a pivotal role in orchestrating physiological metabolic pathways through the production of metabolites like bile acids, choline, short-chain fatty neurotransmitters, thereby establishing dynamic "gut-organ axis" with host. intricate interplay between host is indispensable for health, RNA N6-methyladenosine modification, epigenetic mark on RNA, emerges as key player this process. M6A most prevalent internal modification eukaryotic has garnered significant attention realm epigenetics. Recent findings underscore its potential to influence diversity intestinal barrier function modulating gene expression patterns. Conversely, microbiota, impact landscape cells, may indirectly regulate recruitment activity m6A-modifying enzymes. This review endeavors delve into biological functions m6A consequences injury pathogenesis, elucidating partial possible mechanisms which maintain health homeostasis. Furthermore, it also explores crosstalk them injury, offering novel perspective that deepens our understanding underlying diseases.

Language: Английский

Citations

1
RNA m6A modification in ferroptosis: implications for advancing tumor immunotherapy DOI Creative Commons

Jun-Xiao Shi,

Zhichao Zhang, Hao-zan Yin

et al.

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

Published: Sept. 28, 2024

Language: Английский

Citations

7
The YTH domain‐containing protein family: Emerging players in immunomodulation and tumour immunotherapy targets DOI Creative Commons
Fenghe Li,

Chong Zeng,

Jie Liu

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(8)

Published: Aug. 1, 2024

The modification of N6-methyladenosine (m6A) plays a pivotal role in tumor by altering both innate and adaptive immune systems through various pathways, including the regulation messenger RNA. YTH domain protein family, acting as "readers" m6A modifications, affects RNA splicing, stability, immunogenicity, thereby playing essential roles antitumor immunity. Despite their significance, impact family on initiation progression, well involvement therapy, remains underexplored lacks comprehensive review.

Language: Английский

Citations

4
The role of ferroptosis in colorectal cancer and its potential synergy with immunotherapy DOI Creative Commons
Wei Xia,

Yuanhao Lv,

Yan Zou

et al.

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

Published: Jan. 9, 2025

Colorectal cancer (CRC) is one of the most prevalent and deadly malignancies worldwide. Recently, ferroptosis, a novel form regulated cell death characterized by iron dependency lipid peroxidation, has garnered significant attention from researchers. The mechanisms underlying including intracellular levels, antioxidant system regulation, offer new insights into treatment strategies. This study aims to explore emerging role ferroptosis in context immunotherapy for CRC, highlighting its potential clinical applications. We employed comprehensive review current literature elucidate biological relationship with interplay between immunotherapy. Ferroptosis reshapes tumor microenvironment (TME) regulating metabolism, systems, significantly enhancing efficacy immune checkpoint inhibitors (ICIs). Meanwhile, traditional Chinese medicine therapies promote antitumor immunity modulating TME inducing ferroptosis. Additionally, advances nanotechnology have facilitated precise therapy enabling targeted delivery inducers or immunomodulators, transforming "cold" tumors "hot" further boosting ICI efficacy. comprehensively reviews latest developments immunotherapy, medicine, importance ferroptosis-related biomarkers personalized treatment. In summary, offers promising strategy overcome CRC resistance enhance efficacy, warranting investigation translational application.

Language: Английский

Citations

0
FTO effects the proliferation, invasion, and glycolytic metabolism of colon cancer by regulating PKM2 DOI Creative Commons

Kong‐Yan Zhang,

Fei Zhang, Jiahe Wang

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2025, Volume and Issue: 151(1)

Published: Jan. 16, 2025

Language: Английский

Citations

0
ZHX2 inhibits diabetes-induced liver injury and ferroptosis by epigenetic silence of YTHDF2 DOI Creative Commons
Wei Meng,

Linghua Li

Nutrition and Diabetes, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 22, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common complication of type 2 diabetes mellitus (DM). The transcription factor zinc fingers and homeoboxes (ZHX2) has been implicated in the pathogenesis chronic diseases, yet its precise role underlying mechanism DM-induced hepatic injury remain poorly elucidated. To investigate this, we used high-fat diet (HFD) streptozotocin (STZ) administration to create DM model mice, while high glucose (HG) exposure was simulate vitro. Through various experiments such as luciferase reporter assay, chromatin immunoprecipitation, RNA rescue experiments, aimed uncover mechanisms involving ZHX2. Our findings revealed that ZHX2 lower YTHDF2 higher livers mice HG-induced Huh7 cells. overexpression rescued injury. also reversed ferroptosis vivo Mechanistically, recognized m6A-modified mRNA promoted degradation. In turn, inhibited by binding promoter region. Knockdown led increased cells through activating YTHDF2-induced GPX4 SLC7A11 These highlight involvement ZHX2-YTHDF2-ferroptosis pathway suggest targeting this may hold therapeutic potential for improving injuries.

Language: Английский

Citations

0
Engineering Iridium Nanoclusters for Boosting Ferroptotic Cell Death by Regulating GPX4 and p53 Functions DOI
Xiaoyu Cui, Bin Chen, Ying Chen

et al.

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Abstract Emerging evidence indicates that modulating glutathione peroxidase 4 (GPX4) to induce ferroptosis is a promising strategy for tumor treatment. However, most of the GPX4 small molecule inhibitors face limitations due their poor delivery efficacy and low specificity activation. Herein, ferroptosis‐inducing nanomedicine developed integrates nutlin‐3 with iridium oxide nanoclusters (NUT‐IrO x NCs) enhanced ferroptosis‐driven multimodal therapeutic in colorectal cancer (CRC). This NUT‐IrO NCs can (GSH) depletion via Ir (VI)‐Ir (III) transition, while nutlin‐3, well‐established inhibitor p53‐MDM2 interaction, suppresses GSH production by modulation p53/SLC7A11/xCT signaling pathway. The reduction intracellular results pronounced reductions enzymatic activity, consequently leading lipid peroxidation accumulation further enhancing ferroptosis‐induced CRC therapy. dual‐pronged approach demonstrates robust anticancer effects favorable biocompatibility both vitro vivo models. study provides an effective highlights benefits inhibiting GSH/GPX4 activating multiple regulatory pathways, providing alternative avenue

Language: Английский

Citations

0