PRMT6 facilitates EZH2 protein stability by inhibiting TRAF6-mediated ubiquitination degradation to promote glioblastoma cell invasion and migration DOI Creative Commons
Ji Wang,

Shiquan Shen,

Jian You

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 14, 2024

Abstract Invasion and migration are the key hallmarks of cancer, aggressive growth is a major factor contributing to treatment failure poor prognosis in glioblastoma. Protein arginine methyltransferase 6 (PRMT6), as an epigenetic regulator, has been confirmed promote malignant proliferation GBM cells previous studies. However, effects PRMT6 on cell invasion its underlying mechanisms remain elusive. Here, we report that functions driver element for tumor Bioinformatics analysis glioma sample detection results demonstrated highly expressed mesenchymal subtype or invasive gliomas, significantly negatively correlated with their prognosis. Inhibition (using shRNA inhibitor EPZ020411) reduces in vitro, whereas overexpression produces opposite effects. Then, identified maintains protein stability EZH2 by inhibiting degradation protein, thereby mediating cells. Further mechanistic investigations found inhibits transcription TRAF6 activating histone methylation mark (H3R2me2a), reducing interaction between enhance Xenograft assay HE staining showed expression could vivo, immunohistochemical mouse brain tissue sections also regulatory relationship PRMT6, TRAF6, EZH2. Our findings illustrate suppresses via H3R2me2a facilitate migration. Blocking PRMT6-TRAF6-EZH2 axis promising strategy

Language: Английский

Promising role of protein arginine methyltransferases in overcoming anti-cancer drug resistance DOI Creative Commons
Yongxia Zhu, Tong Xia,

D Chen

et al.

Drug Resistance Updates, Journal Year: 2023, Volume and Issue: 72, P. 101016 - 101016

Published: Nov. 3, 2023

Drug resistance remains a major challenge in cancer treatment, necessitating the development of novel strategies to overcome it. Protein arginine methyltransferases (PRMTs) are enzymes responsible for epigenetic methylation, which regulates various biological and pathological processes, as result, they attractive therapeutic targets overcoming anti-cancer drug resistance. The ongoing small molecules targeting PRMTs has resulted generation chemical probes modulating most facilitated clinical treatment advanced oncology targets, including PRMT1 PRMT5. In this review, we summarize mechanisms underlying protein methylation roles specific driving Furthermore, highlight potential implications PRMT inhibitors decreasing promote formation maintenance drug-tolerant cells via several mechanisms, altered efflux transporters, autophagy, DNA damage repair, stem cell-related function, epithelial-mesenchymal transition, disordered tumor microenvironment. Multiple preclinical trials have demonstrated that inhibitors, particularly PRMT5 can sensitize drugs, chemotherapeutic, targeted therapeutic, immunotherapeutic agents. Combining with existing will be promising approach enhanced knowledge complex functions guide future may help identify new indications.

Language: Английский

Citations

23
Protein arginine methyltransferases (PRMTs): Orchestrators of cancer pathogenesis, immunotherapy dynamics, and drug resistance DOI

Yihang Gao,

Chongchong Feng,

Jingru Ma

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 221, P. 116048 - 116048

Published: Feb. 10, 2024

Language: Английский

Citations

8
circFAM193B interaction with PRMT6 regulates AML leukemia stem cells chemoresistance through altering the oxidative metabolism and lipid peroxidation DOI
Xinyu Yang, Jinting Liu, Wancheng Liu

et al.

Leukemia, Journal Year: 2024, Volume and Issue: 38(5), P. 1057 - 1071

Published: Feb. 29, 2024

Language: Английский

Citations

8
PRMT1 in human neoplasm: cancer biology and potential therapeutic target DOI Creative Commons

Shiquan Shen,

Honglong Zhou,

Zongyu Xiao

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 8, 2024

Abstract Protein arginine methyltransferase 1 (PRMT1), the predominant type I protein methyltransferase, plays a crucial role in normal biological functions by catalyzing methylation of side chains, specifically monomethylarginine (MMA) and asymmetric dimethylarginine (ADMA), within proteins. Recent investigations have unveiled an association between dysregulated PRMT1 expression initiation progression tumors, significantly impacting patient prognosis, attributed to PRMT1’s involvement regulating various facets tumor cell biology, including DNA damage repair, transcriptional translational regulation, as well signal transduction. In this review, we present overview recent advancements research across different types, with specific focus on its contributions proliferation, metastasis, invasion, drug resistance. Additionally, expound dynamic during distinct stages cancer progression, elucidating unique regulatory mechanisms same signaling pathway distinguishing promotive inhibitory effects. Importantly, sought provide comprehensive summary analysis progress contributing deeper understanding tumorigenesis, development, potential treatment strategies.

Language: Английский

Citations

7
PRMT6-mediated transcriptional activation of ythdf2 promotes glioblastoma migration, invasion, and emt via the wnt–β-catenin pathway DOI Creative Commons
Peng Yu,

Tutu Xu,

Wenmeng Ma

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: April 18, 2024

Abstract Background Protein arginine methyltransferase 6 (PRMT6) plays a crucial role in various pathophysiological processes and diseases. Glioblastoma (GBM; WHO Grade 4 glioma) is the most common lethal primary brain tumor adults, with prognosis that extremely poor, despite being less than other systemic malignancies. Our current research finds PRMT6 upregulated GBM, enhancing malignancy. Yet, specifics of PRMT6’s regulatory potential molecular mechanisms GBM remain largely unexplored. Methods expression prognostic significance were assessed using glioma public databases, immunohistochemistry (IHC), immunoblotting. Scratch Transwell assays examined cell migration invasion. Immunoblotting evaluated epithelial-mesenchymal transition (EMT) Wnt-β-catenin pathway-related proteins. Dual-luciferase reporter ChIP-qPCR relationship between YTHDF2. An situ model nude mice vivo conditions. Results Bioinformatics analysis indicates high YTHDF2 correlating poor prognosis. Functional experiments show promote migration, invasion, EMT. Mechanistic reveal CDK9 co-regulate expression. binds promotes degradation negative regulators APC GSK3β mRNA pathway, activating it consequently Conclusions results demonstrate PRMT6-YTHDF2-Wnt-β-Catenin axis EMT vitro vivo, potentially serving as therapeutic target for GBM.

Language: Английский

Citations

7
Neuroprotective effect of apo-9′-fucoxanthinone against cerebral ischemia injury by targeting the PI3K/AKT/GSK-3β pathway DOI
Yu Qi,

Shuhua Tang,

Shengjie Jin

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: 991, P. 177348 - 177348

Published: Feb. 5, 2025

Language: Английский

Citations

0
NSUN4 Facilitates the Activity of Oncogenic Protein CDC20 to Promote NSCLC Development by Mediating m5C Modification of CDC20 mRNA DOI Creative Commons
Zhilong Li,

Wu Xianzhen

Thoracic Cancer, Journal Year: 2025, Volume and Issue: 16(5)

Published: March 1, 2025

5-methylcytosine (m5C) methylation is the crucial posttranscriptional modification of RNA. NSUN4, a methyltransferase for m5C methylation, contributes to lung tumorigenesis. Here, we determined precise action NSUN4 on development non-small cell cancer (NSCLC). and CDC20 mRNA expression was detected by quantitative PCR. Western blot immunohistochemistry were used analysis protein expression. Cell growth, apoptosis, invasiveness, migratory ability, stemness potential evaluated colony formation, flow cytometry, transwell, sphere formation assays. The influence in analyzed using RNA immunoprecipitation (RIP) assay Actinomycin D (Act D) treatment. Subcutaneous xenograft studies performed analyze function vivo. In human NSCLC tumors lines, levels upregulated. inhibition diminished stemness, ability vitro, while increase had opposite effects. A positive association between observed samples. Mechanistically, enhanced stability through modification. depletion significantly counteracted NSUN4-driven phenotype alterations vitro. Additionally, impeded growth A549 subcutaneous xenografts Our findings identify pro-tumorigenic property NSUN4/CDC20 cascade NSCLC. Targeting novel may be promising way combating this deadly disease.

Language: Английский

Citations

0
4-Hydroxydictyolactone alleviates cerebral ischemia injury by regulating neuroinflammation and autophagy via AMPK signaling pathway DOI
Yu Qi,

Haoyun Zhu,

Yinqi Chen

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 135, P. 156157 - 156157

Published: Oct. 19, 2024

Language: Английский

Citations

2
TRIM6 promotes glioma malignant progression by enhancing FOXO3A ubiquitination and degradation DOI Creative Commons

Jingpeng Guo,

Ji Wang, Peng Zhang

et al.

Translational Oncology, Journal Year: 2024, Volume and Issue: 46, P. 101999 - 101999

Published: May 17, 2024

TRIM6, an E3 ubiquitin ligase with tripartite motif, directly targets protein substrates for degradation through ubiquitination. Studies have shown that TRIM6 plays a significant role in tumor development various human malignancies. Thus, the aim of this study was to investigate importance and its associated mechanism promoting progression glioma. The expression prognostic value glioma patients were collected from TCGA CGGA databases. effects on investigated vitro by CCK8, colony formation, wound healing, transwell assays. Co-IP western blot analysis used detect interaction between FOXO3A. verified vivo subcutaneously xenograft models, size, immunohistochemical changes observed. Our tissues revealed high level expression, heightened showed positive correlation unfavorable prognosis among glioma/GBM patients. Through loss-of-function gain-of-function experiments, we observed profound impact proliferation, invasion, migration abilities cells both upon deletion TRIM6. Conversely, overexpression intensified malignant characteristics Additionally, our findings FOXO3A, wherein contributed destabilization FOXO3A ubiquitination subsequent degradation. Experiments conducted rescue affirmed promotion cell is facilitated suppression levels. These observations imply TRIM6-FOXO3A axis could potentially serve as innovative focus intervening

Language: Английский

Citations

1
Dysregulation of arginine methylation in tumorigenesis DOI Creative Commons
Li Xiao,

Yaqiong Song,

Weiwei Mu

et al.

Frontiers in Molecular Biosciences, Journal Year: 2024, Volume and Issue: 11

Published: June 7, 2024

Protein methylation, similar to DNA primarily involves post-translational modification (PTM) targeting residues of nitrogen-containing side-chains and other residues. arginine occurred on residue, is mainly mediated by protein methyltransferases (PRMTs), which are ubiquitously present in a multitude organisms intricately involved the regulation numerous biological processes. Specifically, PRMTs pivotal process gene transcription regulation, function modulation. Abnormal particularly histones, can induce dysregulation expression, thereby leading development cancer. The recent advancements cancer research have had profound impact our understanding abnormal carcinogenesis progression. This review will provide defined overview these progression, with aim augmenting knowledge role progression their potential application therapy.

Language: Английский

Citations

1