Integrative analysis of lysine acetylation-related genes and identification of a novel prognostic model for oral squamous cell carcinoma DOI Creative Commons
Shi‐Zhou Deng, Xuechen Wu, Jiezhang Tang

et al.

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Aug. 29, 2023

Introduction: Oral squamous cell carcinoma (OSCC), which accounts for a high proportion of oral cancers, is characterized by aggressiveness and rising incidence. Lysine acetylation associated with cancer pathogenesis. acetylation-related genes (LARGs) are therapeutic targets potential prognostic indicators in various tumors, including carcinoma. However, systematic bioinformatics analysis the still unexplored. Methods: We analyzed expression 33 effects their somatic mutations on prognosis. Consistent clustering identified two lysine patterns differences between were further evaluated. Least absolute shrinkage selection operator (LASSO) regression was used to develop model using TCGA datasets, then validated gene omnibus (GEO) dataset GSE41613. Results: Patients lower risk scores had better prognoses, both overall cohort within subgroups These patients also "hot" immune microenvironments more sensitive immunotherapy. Disscussion: Our findings offer new classifying determining its prognosis novel insights into diagnosis treatment.

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

30

Histone deacetylase-mediated tumor microenvironment characteristics and synergistic immunotherapy in gastric cancer DOI Creative Commons
Yilin Lin, Xiangxiang Jing, Zhihua Chen

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 13(13), P. 4574 - 4600

Published: Jan. 1, 2023

Background: Studies have shown that the expression of histone deacetylases (HDACs) is significantly related to tumor microenvironment (TME) in gastric cancer. However, a single molecule or several molecules does not accurately reflect TME characteristics guide immunotherapy Methods: We constructed an HDAC score (HDS) based on level HDACs. The single-cell transcriptome was used analyze underlying factors contributing differences immune infiltration between patients with high and low HDS. In vitro vivo experiments validated strategy transforming cold tumors into hot immunotherapy. Results: According HDACs, we HDS model characterize TME. found had stronger immunogenicity could benefit more from than those score. AUC value combined positive (CPS)for predicting efficacy as 0.96. By paired bulk sequencing analysis, levels CD4+ T cells, CD8+ cells NK were decreased group, which may be induced by MYH11+ fibroblasts, CD234+ endothelial CCL17+ pDCs via MIF signaling pathway. Inhibition pathway confirmed potentially enhance infiltration. addition, our analysis revealed GPX4 inhibitors might effective for knockout inhibited PD-L1 promoted activation cells. Conclusion: This evaluate predict efficacy. important synergistic

Language: Английский

Citations

30

Single-nucleus multiomics reveals the gene regulatory networks underlying sex determination of murine primordial germ cells DOI Creative Commons
Adriana K. Alexander, Karina F. Rodriguez, Yuying Chen

et al.

eLife, Journal Year: 2025, Volume and Issue: 13

Published: March 10, 2025

Accurate specification of female and male germ cells during embryonic development is critical for sexual reproduction. Primordial (PGCs) are the bipotential precursors mature gametes that commit to an oogenic or spermatogenic fate in response sex-determining cues from fetal gonad. The processes required PGCs integrate respond signals somatic environment gonads not well understood. In this study, we developed first single-nucleus multiomics map chromatin accessibility gene expression murine PGC both XX XY embryos. Profiling cell-type-specific transcriptomes regions open same cell captured molecular signatures networks underlying sex determination. Joint RNA ATAC data single resolved previously unreported subpopulations cataloged a multimodal reference atlas differentiating clusters. We discovered regulatory element precedes development, suggesting changes may prime lineage commitment prior differentiation. Similarly, found dimorphism increased temporally PGCs. Combining sequencing data, computationally mapped cohort transcription factors regulate sexually dimorphic genes For example, enriched factors, TFAP2c, TCFL5, GATA2, MGA, NR6A1, TBX4, ZFX. Sex-specific enrichment forkhead-box POU6 families was also observed Finally, determined temporal patterns WNT, BMP, RA signaling determination, our discovery analyses identified potentially new communication pathways between supporting Our results illustrate diversity involved programming toward sex-specific fate.

Language: Английский

Citations

1

The role of protein acetylation in carcinogenesis and targeted drug discovery DOI Creative Commons
Jingru Yang, Cong Song, Xianquan Zhan

et al.

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 12, 2022

Protein acetylation is a reversible post-translational modification, and involved in many biological processes cells, such as transcriptional regulation, DNA damage repair, energy metabolism, which an important molecular event associated with wide range of diseases cancers. dynamically regulated by histone acetyltransferases (HATs) deacetylases (HDACs) homeostasis. The abnormal level might lead to the occurrence deterioration cancer, closely related various pathophysiological characteristics malignant phenotypes, promotes cancer cells adapt tumor microenvironment. Therapeutic modalities targeting protein are potential therapeutic strategy. This article discussed roles pathology drugs acetylation, offers contributions clarification carcinogenesis, discovery for cancers, lays foundation precision medicine oncology.

Language: Английский

Citations

29

MicroRNA-383: A tumor suppressor miRNA in human cancer DOI Creative Commons
Abdollah Jafarzadeh,

Majid Noori,

Shaghayegh Sarrafzadeh

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Oct. 13, 2022

Downregulated expression of anti-tumor miR-383 has been found in many kinds cancer. MiR-383 family members can directly target the 3′-untranslated region (3′-UTR) mRNA some pro-tumor genes to attenuate several cancer-related processes, including cell proliferation, invasion, migration, angiogenesis, immunosuppression, epithelial-mesenchymal transition, glycolysis, chemoresistance, and development cancer stem cells, whilst promoting apoptosis. Functionally, operates as a tumor inhibitor miRNA types cancer, breast hepatocellular carcinoma, gastric pancreatic colorectal esophageal lung head neck glioma, medulloblastoma, melanoma, prostate cervical oral squamous thyroid B-cell lymphoma. Both effects have attributed ovarian However, only were reported cholangiocarcinoma. The restoration could be considered possible treatment for This review discusses human cancers, emphasizing their downstream potential approaches.

Language: Английский

Citations

25

Oxidized low-density lipoprotein regulates macrophage polarization in atherosclerosis DOI

Yonghang He,

Tingting Liu

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 120, P. 110338 - 110338

Published: May 19, 2023

Language: Английский

Citations

16

MicroRNA-Mediated Regulation of Histone-Modifying Enzymes in Cancer: Mechanisms and Therapeutic Implications DOI Creative Commons
Joanna Szczepanek, Andrzej Tretyn

Biomolecules, Journal Year: 2023, Volume and Issue: 13(11), P. 1590 - 1590

Published: Oct. 28, 2023

In the past decade, significant advances in molecular research have provided a deeper understanding of intricate regulatory mechanisms involved carcinogenesis. MicroRNAs, short non-coding RNA sequences, exert substantial influence on gene expression by repressing translation or inducing mRNA degradation. context cancer, miRNA dysregulation is prevalent and closely associated with various stages carcinogenesis, including initiation, progression, metastasis. One crucial aspect cancer phenotype activity histone-modifying enzymes that govern chromatin accessibility for transcription factors, thus impacting expression. Recent studies revealed miRNAs play role modulating these enzymes, leading to implications genes related proliferation, differentiation, apoptosis cells. This article provides an overview current which regulate cancer. Both direct indirect through enzyme are discussed. Additionally, potential therapeutic arising from manipulation selectively impact presented. The insights this analysis hold promise, suggesting utility as tools precise regulation chromatin-related processes A contemporary focus opens pathways can effectively control tumor cell growth dissemination.

Language: Английский

Citations

14

The role of histone acetylation in transcriptional regulation and seed development DOI Open Access
Yan Chen, Peiguo Guo, Zhicheng Dong

et al.

PLANT PHYSIOLOGY, Journal Year: 2023, Volume and Issue: 194(4), P. 1962 - 1979

Published: Nov. 18, 2023

Abstract Histone acetylation is highly conserved across eukaryotes and has been linked to gene activation since its discovery nearly 60 years ago. Over the past decades, histone evidenced play crucial roles in plant development response various environmental cues. Emerging data indicate that one of defining features “open chromatin,” while role transcription remains controversial. In this review, we briefly describe acetylation, mechanism regulating yeast mammals, summarize research progress acetylation. Furthermore, also emphasize effect on seed potential use breeding. A comprehensive knowledge might provide new more flexible perspectives enhance crop yield stress resistance.

Language: Английский

Citations

12

Butyrate Prevents Obesity Accompanied by HDAC9-Mediated Browning of White Adipose Tissue DOI Creative Commons
Jing Yang, Guoli Li, Shan Wang

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 260 - 260

Published: Jan. 21, 2025

Background/Objectives: Mounting evidence indicates that the short-chain fatty acid butyrate protects against obesity and associated comorbidities, partially through induction of adipose tissue thermogenesis. However, effects on white (WAT) browning its molecular mechanism are still elusive. The objective this study was to investigate butyrate-induced thermogenesis in underlying mechanism. Methods: We studied diet-induced humanized APOE*3-Leiden.CETP transgenic mouse model explored factors related browning. Specifically, mice were challenged with a high-fat diet supplemented butyrate. Adiposity measured assess development. Energy metabolism detected using an indirect calorimetry system. RNA-seq analysis conducted analyze transcription landscape WAT responsible targets. Furthermore, revealed verified vitro. Results: Butyrate alleviated promoted energy expenditure accompanied by brown activation Mechanistically, downregulated HDAC9 WAT. Additionally, decreased while increasing Inhibition TMP269 thermogenic gene expression, mimicking Conclusions: decreasing expression inducing This reveals new whereby activates adaptive provides insights for development weight-loss drugs targeting HDAC9.

Language: Английский

Citations

0

Single-nucleus multiomics reveals the gene-regulatory networks underlying sex determination of murine primordial germ cells DOI Open Access
Adriana K. Alexander, Karina F. Rodriguez, Yuying Chen

et al.

Published: Jan. 29, 2025

Accurate specification of female and male germ cells during embryonic development is critical for sexual reproduction. Primordial (PGCs) are the bipotential precursors mature gametes that commit to an oogenic or spermatogenic fate in response sex-determining cues from fetal gonad. The processes required PGCs integrate respond signals somatic environment gonads not understood. In this study, we developed first single-nucleus multiomics map chromatin accessibility gene expression murine PGC both XX XY embryos. Profiling cell-type specific transcriptomes regions open same cell captured molecular signatures networks underlying sex determination. Joint RNA ATAC data single resolved previously unreported subpopulations cataloged a multimodal reference atlas differentiating clusters. We discovered regulatory element precedes development, suggesting changes may prime lineage commitment prior differentiation. Similarly, found dimorphism increased temporally PGCs. Combining sequencing data, computationally mapped cohort transcription factors regulate sexually dimorphic genes For example, enriched factors, TFAP2c, TCFL5, GATA2, MGA, NR6A1, TBX4, ZFX. Sex-specific enrichment forkhead-box POU6 families was also observed Finally, determined temporal patterns WNT, BMP, RA signaling determination, our discovery analyses identified potentially new communication pathways between supporting Our results illustrate diversity involved programming towards sex-specific fate.

Language: Английский

Citations

0