Methionine-driven YTHDF1 expression facilitates bladder cancer progression by attenuating RIG-I-modulated immune responses and enhancing the eIF5B-PD-L1 axis DOI Creative Commons
Anze Yu, Liangmin Fu,

Lanyu Jing

et al.

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 13, 2024

Abstract The impact of amino acids on tumor immunotherapy is gradually being uncovered. In this study, we screened various essential and non-essential found that methionine enhances mRNA methylation reduced the activation Type I interferon pathway in bladder cancer. Through RNA sequencing, point mutations, MB49 mouse models, single-cell demonstrated high levels elevate expression m 6 A reader YTHDF1, promoting degradation RIG-I, thereby inhibiting RIG-I/MAVS-mediated IFN-I reducing efficacy immunotherapy. Additionally, immunoprecipitation mass spectrometry revealed YTHDF1 binds to eukaryotic translation initiation factor eIF5B, which acts PD-L1 enhance its promote immune evasion. By intravesical administration oncolytic bacteria VNP20009, effectively depleted locally, significantly prolonging survival enhancing cell infiltration differentiation within tumors. Multiplex immunofluorescence assays cancer patients confirmed our findings. Our research elucidates two mechanisms by inhibits proposes a targeted depletion strategy advances while minimizing nutritional patients.

Language: Английский

Pyroptotic cell death: an emerging therapeutic opportunity for radiotherapy DOI Creative Commons
Hongbin Li,

Tiantian Yang,

Jialin Zhang

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 16, 2024

Abstract Pyroptotic cell death, an inflammatory form of programmed death (PCD), is emerging as a potential therapeutic opportunity for radiotherapy (RT). RT commonly used cancer treatment, but its effectiveness can be limited by tumor resistance and adverse effects on healthy tissues. Pyroptosis, characterized swelling, membrane rupture, release pro-inflammatory cytokines, has been shown to enhance the immune response against cells. By inducing pyroptotic in cells, treatment outcomes stimulating anti-tumor responses improving overall efficacy RT. Furthermore, danger signals from cells promote recruitment activation leading systemic that may target distant metastases. Although further research needed fully understand mechanisms optimize use RT, it holds promise novel strategy outcomes. This review aims synthesize recent regulatory underlying radiation-induced pyroptosis elucidate significance this process The insights gained analysis inform strategies tumors.

Language: Английский

Citations

11
An Enzymatically Activated and Catalytic Hairpin Assembly-Driven Intelligent AND-Gated DNA Network for Tumor Molecular Imaging DOI
Mengxin Zhang, Yingyu Zhang, Xianwei Zhang

et al.

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(24), P. 10084 - 10091

Published: June 5, 2024

Due to the potential off-tumor signal leakage and limited biomarker content, there is an urgent need for stimulus-responsive amplification-based tumor molecular imaging strategies. Therefore, two tetrahedral framework DNA (tFNA-Hs), tFNA-H1AP, tFNA-H2, were rationally engineered form a polymeric tFNA network, termed intelligent in AND-gated manner. The network was designed tumor-specific by leveraging elevated expression of apurinic/apyrimidinic endonuclease 1 (APE1) cytoplasm instead normal cells high miRNA-21 cytoplasm. activation tFNA-H1AP can be achieved through specific recognition cleavage APE1, targeting site (AP site) modified within stem region hairpin (H1AP). Subsequently, facilitates hybridization activated H1AP on with 2 (H2) triggering catalytic assembly (CHA) reaction that opens at vertices bind H2 tFNA-H2 generate fluorescence signals. Upon completion hybridization, released, initiating subsequent cycle CHA reaction. achieve vivo also enables risk stratification neuroblastoma patients.

Language: Английский

Citations

11
Imaging-guided companion diagnostics in radiotherapy by monitoring APE1 activity with afterglow and MRI imaging DOI Creative Commons
Renye Yue, Zhe Li, Huiyi Liu

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 27, 2024

Companion diagnostics using biomarkers have gained prominence in guiding radiotherapy. However, biopsy-based techniques fail to account for real-time variations target response and tumor heterogeneity. Herein, we design an activated afterglow/MRI probe as a companion tool dynamically assessing biomarker apurinic/apyrimidinic endonuclease 1(APE1) during radiotherapy vivo. We employ ultrabright afterglow nanoparticles ultrasmall FeMnOx dual contrast agents, significantly broadening signal change range enhancing the sensitivity of APE1 imaging (limit detection: 0.0092 U/mL 0.16 MRI). devise longitudinally transversely subtraction-enhanced (L&T-SEI) strategy markedly enhance MRI signal-to-noise ratio between normal tissue living female mice. The combined facilitate both anatomical functional activity. This enables correlation signals with expression, radiation dosage, intratumor ROS, DNA damage, enabling early prediction outcomes (as 3 h), preceding size reduction (6 days). By monitoring levels, this allows sensitive detection liver organ injury, outperforming histopathological analysis. Furthermore, evaluates expression radiation-induced abscopal effects provides insights into underlying mechanisms, supports development treatment protocols. are promising radiotherapy, but normally detect authors report

Language: Английский

Citations

11
An enzymatically activated self-powered and self-recycled strategy for in situ tumor cell-specific molecular imaging DOI
Mengxin Zhang, Yingyu Zhang, Xianwei Zhang

et al.

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 489, P. 151226 - 151226

Published: April 15, 2024

Language: Английский

Citations

4
Controlled activation of a DNA walker driven by mismatched catalytic hairpin assembly for microRNA imaging in cancer cells and clinical samples DOI
Liuting Mo,

Shiya Tang,

Fenghua Meng

et al.

Sensors and Actuators B Chemical, Journal Year: 2025, Volume and Issue: 437, P. 137747 - 137747

Published: April 10, 2025

Language: Английский

Citations

0
(-)-Epicatechin regulates the resistance of lung adenocarcinoma cells to radiotherapy through the downregulation of FOXM1 DOI
Jie Xia,

Hongying Xu,

Sihan Zhou

et al.

In Vitro Cellular & Developmental Biology - Animal, Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Language: Английский

Citations

0
Isoliensinine exerts antitumor effects in lung adenocarcinoma by inhibiting APEX1-driven ROS production DOI Creative Commons
Cheng Chen,

Chenying Shu,

Dan Shen

et al.

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

Published: May 27, 2025

Introduction Lung cancer is considered to be the world’s leading malignancy in morbidity and mortality, despite great efforts treat it no effective treatment has yet been found. Isoliensinine a natural small-molecule drug with potent anti-tumor activity several cell lines. Here, we have shown that exhibits against lung adenocarcinoma (LUAD) both vitro vivo . Methods The biological functions of LUAD cells were investigated using CCK8 assay, colony formation, transwell assays flow cytometry assays. DARTS assay was used validate targets screened by site prediction molecular docking. efficacy analyzed xenograft tumor model. Results IC 50 6.98 μM, 17.24 μM 16.00 H1299, A549, H1650 lines while 28.65 BEAS-2B cells. inhibits proliferation, migration, invasion arrests cycle promotes apoptosis attenuates growth murine mode. Mechanistically, interacted directly APEX1, inhibited APEX1 protein levels, promoted ROS generation. Knockdown reverses effect on Discussion exerts antitumor effects through inhibition driven production, therefore, may represent new candidate LUAD.

Language: Английский

Citations

0
Unveiling the therapeutic potential: KBU2046 halts triple-negative breast cancer cell migration by constricting TGF-β1 activation <i>in vitro</i> DOI Creative Commons

JINXIA CHEN,

SULI DAI,

Geng Zhang

et al.

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Journal Year: 2024, Volume and Issue: 0(0), P. 1 - 10

Published: Jan. 1, 2024

Triple-negative breast cancer (TNBC) is a heterogeneous, recurring characterized by high rate of metastasis, poor prognosis, and lack efficient therapies. KBU2046, small molecule inhibitor, can inhibit cell motility in malignant tumors, including cancer. However, the specific targets corresponding mechanism its function remain unclear.

Language: Английский

Citations

1
Inhibition of non-small cell lung cancer metastasis by knocking down APE1 through regulating myeloid-derived suppressor cells-induced immune disorders DOI Creative Commons
Zhenlong Zhang,

Yu‐Chen Lin,

Xiaojie Pan

et al.

Aging, Journal Year: 2024, Volume and Issue: 16(12), P. 10435 - 10445

Published: June 14, 2024

Background: Non-small cell lung cancer (NSCLC) represents a highly immunogenic malignancy. Immunologic tolerance facilitated by myeloid-derived suppressor cells (MDSCs) is implicated in primary or secondary resistance mechanisms NSCLC. The potential role of APE1 regulating NSCLC metastasis targeting MDSCs remains uncertain. Methods: This study utilized plasmid, Plxpsp-mGM-CSF, to induce elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) expression A549 cells. Tumor transplantation experiments involved A549, A549+GM-CSF, and A549+GM-CSF-siAPE1 lines. Evaluation encompassed MDSCs, Treg cells, IgG, CD3, CD8 levels. Results: Notably, tissues displayed markedly reduced expression. siAPE1 transfection significantly curtailed tumor growth compared the A549+GM-CSF group. knockdown orchestrated immune system modulation mice, characterized diminished but augmented CD8. Additionally, led levels pro-MDSC cytokines (HGF, CCL5, IL-6, CCL12) concurrent upregulation anti-MDSC cytokine IL-1ra. Furthermore, impeded viability both H1650 Conclusions: Transplantation A549-GM-CSF amplified MDSC levels, fostering accelerated growth, while mitigating through hindered progression alleviated inflammatory infiltration tissues. Strategies APE1/MDSC axis offer promising approach for prevention treatment, presenting novel insights management.

Language: Английский

Citations

1
Enzymatically Cyclic Activated Biosensor Based on a Tetrahedral DNA Framework for Precise Tumor in Situ Molecular Imaging DOI

Muchun Yu,

Yingyu Zhang, Mengxin Zhang

et al.

ACS Sensors, Journal Year: 2024, Volume and Issue: 9(10), P. 5302 - 5311

Published: Oct. 10, 2024

The development of stimulus-responsive and amplification-based strategies is crucial for achieving improved spatial specificity enhanced sensitivity in tumor molecular imaging, addressing challenges such as off-tumor signal leakage limited biomarker content. Therefore, a cyclically activated enzymatic biosensor based on the modification an AP site within tetrahedral framework DNA (AP-tFNA) was rationally developed cell-specific imaging using endogenous enzyme apurinic/apyrimidinic endonuclease 1 (APE1) target, exhibiting superior high sensitivity. APE1, which predominantly localizes nucleus normal cells but exhibits cytosolic expression cancer cells, can specifically recognize cleave AP-tFNA, resulting separation fluorophore quenching group, thereby inducing fluorescence signal. Additionally, upon completion excision one APE1 released, initiating subsequent cycle hydrolytic cleavage reactions. experimental results demonstrated that AP-tFNA enables precise differentiation both

Language: Английский

Citations

1