Identification of ETV5 as a prognostic marker related to epigenetic modification in pan-cancer and facilitates tumor progression in hepatocellular carcinoma DOI Creative Commons
Hongmeng Su,

Luyu Zhao,

Fang Tian

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 29, 2024

ETS variant transcription factor 5 (ETV5), a master during development, exerts vital function on the occurrence and progression of various cancers. In order to systematically analyze explore ETV5 potential specific regulatory mechanisms in pan-cancer, RNA sequencing data clinicopathological features patients with tumors were obtained through Cancer Genome Atlas (TCGA) Genotype-Tissue Expression (GTEx) databases, an integrated mining analysis was carried out, including association expression patient prognosis, drug sensitivity epigenetic modification. The results revealed that abnormally highly expressed resulted unfavorable prognosis differential multiple malignancies, its associated modification modulators EZH2. related genes enriched tumorigenesis biological processes signaling pathways. hepatocellular carcinoma, correlated patients' tumor pathological stage adverse outcome patients. Our further experiments evidences indicated facilitated cell proliferation reduced GSK126 via regulating Collectively, this study comprehensively elucidates carcinogenic effects molecular provides theoretical basis guidance for diagnosis, targeted therapy clinical research.

Language: Английский

YTHDF2 Is a Therapeutic Target for HCC by Suppressing Immune Evasion and Angiogenesis Through ETV5/PD‐L1/VEGFA Axis DOI Creative Commons
Jingyuan Wen, Xue Lin, Wei Yi

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)

Published: Jan. 21, 2024

Abstract N6‐methyladenosine (m 6 A) modification orchestrates cancer formation and progression by affecting the tumor microenvironment (TME). For hepatocellular carcinoma (HCC), immune evasion angiogenesis are characteristic features of its TME. The role YTH RNA binding protein 2 (YTHDF2), as an m A reader, in regulating HCC TME not fully understood. Herein, it is discovered that trimethylated histone H3 lysine 4 27 acetylation promoter region YTHDF2 enhanced expression HCC, upregulated predicted a worse prognosis. Animal experiments demonstrated Ythdf2 depletion inhibited spontaneous formation, while overexpression promoted xenografted progression. Mechanistically, recognized 5′‐untranslational ETS variant transcription factor 5 (ETV5) mRNA recruited eukaryotic translation initiation 3 subunit B to facilitate translation. Elevated ETV5 induced programmed death ligand‐1 vascular endothelial growth A, thereby promoting angiogenesis. Targeting via small interference RNA‐containing aptamer/liposomes successfully both Together, this findings reveal potential application prognosis targeted treatment.

Language: Английский

Citations

26
E-twenty-six-specific sequence variant 5 (ETV5) facilitates hepatocellular carcinoma progression and metastasis through enhancing polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC)-mediated immunosuppression DOI
Zerui Zhang, Wenjie Huang,

Dian Hu

et al.

Gut, Journal Year: 2025, Volume and Issue: unknown, P. gutjnl - 333944

Published: Feb. 27, 2025

Background Despite the success of immune checkpoint blockade, a lack understanding hepatocellular carcinoma (HCC) microenvironment impedes its development. Objective We aim to elucidate essential function E-twenty-six-specific sequence variant 5 (ETV5) in regulating HCC. Design Humanised mouse models, murine orthotopic models and diethylnitrosamine/carbon tetrachloride (DEN/CCl 4 )-induced HCC were used examine ETV5. The downstream targets ETV5 screened using chromatin immunoprecipitation sequencing, CUT&Tag RNA sequencing. Immune cells examined flow cytometry immunofluorescence. S100 calcium-binding protein A9 (S100A9) was targeted by neutralising antibodies. Results Overexpression facilitated metastasis escape recruiting enhancing immunosuppressive capabilities polymorphonuclear myeloid-derived suppressor (PMN-MDSCs). Mechanistically, transactivated programmed death ligand 1 (PD-L1) S100A9 expression. Inhibition or myeloid-specific knockout toll-like receptor (TLR4)/receptor for advanced glycation endproducts (RAGE), receptors S100A9, impeded ETV5-induced PMN-MDSC recruitment. Meanwhile, within tumour elevated expression via extracellular signal-regulated kinase (ERK)/nuclear factor-kappa B pathway. Additionally, transcriptionally upregulated PD-L1 MDSCs as well, thereby augmenting their functions. Myeloid-specific Etv5 attenuated progression. developed monoclonal neutralising-S100A9 antibodies that effectively inhibited ETV5-mediated infiltration. Synergistic application anti-S100A9 TLR4/RAGE inhibitors with anti-PD-L1 therapy significantly suppressed Conclusion facilitates progression promoting recruitment, infiltration activation PMN-MDSCs. holds great promise an effective combinational treatment strategy ETV5-positive

Language: Английский

Citations

1
Harnessing Immunotherapy for Hepatocellular Carcinoma: Principles and Emerging Promises DOI

Hossein Miri,

Payman Rahimzadeh,

Mehrdad Hashemi

et al.

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: unknown, P. 155928 - 155928

Published: March 1, 2025

Language: Английский

Citations

1
Role of m6A modifications in immune evasion and immunotherapy DOI

Chunyu Wu,

Lvyuan Li,

Qiling Tang

et al.

Medical Oncology, Journal Year: 2024, Volume and Issue: 41(6)

Published: May 18, 2024

Language: Английский

Citations

6
m6A modification of VEGFA mRNA by RBM15/YTHDF2/IGF2BP3 contributes to angiogenesis of hepatocellular carcinoma DOI
Xiaoxin Xu,

Shuxiang Wu,

Yi Zhang

et al.

Molecular Carcinogenesis, Journal Year: 2024, Volume and Issue: 63(11), P. 2174 - 2189

Published: Aug. 2, 2024

Vascular endothelial growth factor A (VEGFA) plays a critical role as potent angiogenesis and is highly expressed in hepatocellular carcinoma (HCC). Although the expression of VEGFA has been strongly linked to aggressive nature HCC, specific posttranscriptional modifications that might contribute HCC are not yet well understood. In this study, we aimed investigate epitranscriptome regulation HCC. comprehensive analysis integrating MeRIP-seq, RNA-seq, crosslinking-immunprecipitation-seq data revealed was hypermethylated identified potential m6A regulators including methyltransferase complex component RBM15 two readers, YTHDF2 IGF2BP3. Through rigorous cell molecular biology experiments, validated key responsible for methylation VEGFA, which subsequently recognized stabilized by IGF2BP3 YTHDF2, leading enhanced VEGFA-related functions such human umbilical vascular cells (HUVEC) migration tube formation. xenograft model, knockdown RBM15, IGF2BP3, or resulted reduced accompanied significant inhibition tumor closely associated with angiogenesis. Furthermore, our clinical samples positive correlations between levels YTHDF2. Collectively, these findings offer novel insights into modulation provide avenues alternative approaches antiangiogenesis therapy targeting VEGFA.

Language: Английский

Citations

4
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
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
m6A epitranscriptomic modification in hepatocellular carcinoma: implications for the tumor microenvironment and immunotherapy DOI Creative Commons
Yong Li, Qingbin Liu, Xianying Li

et al.

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

Published: Feb. 17, 2025

Hepatocellular carcinoma (HCC) is the most prevalent primary liver malignancy and a leading cause of cancer-related deaths globally. The asymptomatic progression early-stage HCC often results in diagnosis at advanced stages, significantly limiting therapeutic options worsening prognosis. Immunotherapy, with immune checkpoint inhibitors (ICIs) forefront, has revolutionized treatment. Nevertheless, tumor heterogeneity, evasion, presence immunosuppressive components within microenvironment (TIME) continue to compromise its efficacy. Furthermore, resistance or non-responsiveness ICIs some patients underscores urgent need unravel complexities TIME design innovative strategies that enhance immunotherapeutic outcomes. Emerging evidence revealed pivotal role N6-methyladenosine (m6A), prominent RNA methylation modification, shaping HCC. By regulating stability translation, m6A influences immune-related factors, including cytokines molecules. This modification governs PD-L1 expression, facilitating escape contributing against ICIs. Advances this field have also identified m6A-related regulators as promising biomarkers for predicting immunotherapy response potential targets optimizing treatment review examines regulatory mechanisms HCC, focus on impact cells cytokine dynamics. It explores targeting pathways improve efficacy outlines emerging directions future research. These insights aim provide foundation developing novel overcome advance

Language: Английский

Citations

0
NAD+ Metabolism Reprogramming Drives SIRT1‐Dependent Deacetylation Inducing PD‐L1 Nuclear Localization in Cervical Cancer DOI Creative Commons
Xinyi Lu,

Pingping Jin,

Qianyun Tang

et al.

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

Published: Feb. 23, 2025

Abstract Cervical cancer (CC) is a major health threat to women, with immunotherapies targeting the programmed death receptor 1/programmed ligand 1(PD‐1/PD‐L1) axis showing promise but encountering resistance in significant patient population. This has driven critical quest uncover underlying mechanisms. study uncovers novel metabolic involving nicotinamide adenine dinucleotide (NAD + ) salvage pathway enzyme phosphoribosyltransferase (NAMPT) and deacetylase Sirtuin 1 (SIRT1), which regulates PD‐L1 expression nuclear localization CC. may be key factor contributing observed immunotherapy. reveals that overexpression cancers regulated by both transcriptional post‐transcriptional processes. Acetyl‐proteomic analysis pinpoints SIRT1 as central regulator deacetylation of histone H3 at lysines 27, influence subcellular distribution. finding epigenetic control immune checkpoint proteins pathways, offering new perspective on regulation PD‐L1. The identification NAMPT/SIRT1 suggests this enhance therapeutic responses.

Language: Английский

Citations

0
The role of YTHDF2 in anti-tumor immunity DOI Creative Commons
Leying Zhang, Cunte Chen, Jia Feng

et al.

Cell investigation., Journal Year: 2025, Volume and Issue: 1(1), P. 100008 - 100008

Published: Feb. 26, 2025

Language: Английский

Citations

0