NAT10 Knockdown Improves Cisplatin Sensitivity in Non‐Small Cell Lung Cancer by Inhibiting the TRIM44/PI3K/AKT Pathway DOI Creative Commons

Qi Sun,

Xiansong Yang,

Ye Wang

et al.

Thoracic Cancer, Journal Year: 2025, Volume and Issue: 16(9)

Published: May 1, 2025

ABSTRACT Background Non‐small cell lung cancer (NSCLC) is a leading cause of cancer‐related deaths worldwide, and cisplatin (DDP) resistance remains significant challenge in NSCLC treatment. Methods Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was used to analyze NAT10 tripartite motif containing 44 (TRIM44) mRNA levels. Western blotting assay detect protein expression. Cell viability analyzed by counting kit‐8 assay. proliferation, apoptosis, invasion, stem‐like traits were assessed using 5‐Ethynyl‐2′‐deoxyuridineassay, flow cytometry, Transwell invasion assay, sphere formation respectively. The association between TRIM44 identified an RNA immunoprecipitation A xenograft mouse model established evaluate the effect silencing on DDP sensitivity vivo. Results expression upregulated DDP‐resistant tissues cells. knockdown enhanced cells, accompanied decreased multidrug 1 (MDR1). also inhibited while inducing apoptosis. However, overexpression displayed opposite effects. Moreover, maintained stability ac4C‐dependent manner. reversed knockdown‐induced effects malignant progression In addition, inactivated PI3K/AKT pathway regulating treatment inhibitor, LY294002, mitigated progression. Further, improved tumors Conclusion inhibiting TRIM44/PI3K/AKT pathway, which may have clinical implications for overcoming

Language: Английский

Role of NAT10-mediated ac4C acetylation of ENO1 mRNA in glycolysis and apoptosis in non-small cell lung cancer cells DOI Creative Commons
Yan Yuan, Na Li,

Jingui Zhu

et al.

BMC Pulmonary Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 13, 2025

Language: Английский

Citations

1
Remodelin delays non‐small cell lung cancer progression by inhibiting NAT10 via the EMT pathway DOI
Quanwei Guo, Weijun Yu, Jianfeng Tan

et al.

Cancer Medicine, Journal Year: 2024, Volume and Issue: 13(11)

Published: June 1, 2024

Lung cancer remains the foremost reason of cancer-related mortality, with invasion and metastasis profoundly influencing patient prognosis. N-acetyltransferase 10 (NAT10) catalyzes exclusive N (4)-acetylcytidine (ac4C) modification in eukaryotic RNA. NAT10 dysregulation is linked to various diseases, yet its role non-small cell lung (NSCLC) unclear. Our study delves into clinical significance functional aspects NSCLC.

Language: Английский

Citations

5
RNA N4‐acetylcytidine modification and its role in health and diseases DOI Creative Commons
Qiang Wang,

Yixiao Yuan,

Qiang Zhou

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 1, 2025

Abstract N4‐acetylcytidine (ac4C) modification is a crucial RNA widely present in eukaryotic RNA. Previous studies have demonstrated that ac4C plays pivotal role viral infections. Despite numerous highlighting the strong correlation between and cancer progression, its detailed roles molecular mechanisms normal physiological processes progression remain incompletely understood. This review first outlines key regulatory enzyme mediating modification, N‐acetyltransferase 10 (NAT10), including critical regulating stability, transcriptional efficiency, translational fidelity. Additionally, it systematically summarizes essential functions of biological processes, stem cell fate determination, spermatogenesis oogenesis, embryonic development, cellular senescence, bone remodeling. Furthermore, this delves into central malignant proliferation, cycle arrest, EMT, drug resistance, death, metabolism, tumor immunotherapy. It also emphasizes potential NAT10 as prognostic biomarker therapeutic target for disease treatment. In summary, clarifies multifaceted both health explores NAT10‐targeted therapies with aim advancing research improving patient outcomes.

Language: Английский

Citations

0
NAT10 promotes radiotherapy resistance in non-small cell lung cancer by regulating KPNB1-mediated PD-L1 nuclear translocation DOI Creative Commons

Dagao Zhu,

Mingliang Lu,

Haiying Cheng

et al.

Open Life Sciences, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 1, 2025

Radiotherapy (RT) resistance in non-small cell lung cancer (NSCLC) is a significant contributor to tumor recurrence. NAT10, an enzyme that catalyzes ac4C RNA modification, has unclear role RT resistance. This study aimed explore the function of NAT10 NSCLC. RT-resistant NSCLC lines (PC9R and A549R) were established through repeated irradiation. The impact on cellular immunity was evaluated by measuring immune populations, cytotoxicity levels, markers dysfunction. Results demonstrated elevated levels cells. Knockdown suppressed proliferation enhanced PC9R A549R cells upregulating TNF-α IFN-γ while downregulating PD-1 TIM-3. Mechanistically, mediated NAT10-dependent modification KPNB1. Furthermore, KPNB1 facilitated PD-L1 nuclear translocation, promoting escape Overexpression but impaired In conclusion, this demonstrates upregulates expression thereby via translocation. These findings reveal novel mechanism underlying

Language: Английский

Citations

0
NAT10 Knockdown Improves Cisplatin Sensitivity in Non‐Small Cell Lung Cancer by Inhibiting the TRIM44/PI3K/AKT Pathway DOI Creative Commons

Qi Sun,

Xiansong Yang,

Ye Wang

et al.

Thoracic Cancer, Journal Year: 2025, Volume and Issue: 16(9)

Published: May 1, 2025

ABSTRACT Background Non‐small cell lung cancer (NSCLC) is a leading cause of cancer‐related deaths worldwide, and cisplatin (DDP) resistance remains significant challenge in NSCLC treatment. Methods Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was used to analyze NAT10 tripartite motif containing 44 (TRIM44) mRNA levels. Western blotting assay detect protein expression. Cell viability analyzed by counting kit‐8 assay. proliferation, apoptosis, invasion, stem‐like traits were assessed using 5‐Ethynyl‐2′‐deoxyuridineassay, flow cytometry, Transwell invasion assay, sphere formation respectively. The association between TRIM44 identified an RNA immunoprecipitation A xenograft mouse model established evaluate the effect silencing on DDP sensitivity vivo. Results expression upregulated DDP‐resistant tissues cells. knockdown enhanced cells, accompanied decreased multidrug 1 (MDR1). also inhibited while inducing apoptosis. However, overexpression displayed opposite effects. Moreover, maintained stability ac4C‐dependent manner. reversed knockdown‐induced effects malignant progression In addition, inactivated PI3K/AKT pathway regulating treatment inhibitor, LY294002, mitigated progression. Further, improved tumors Conclusion inhibiting TRIM44/PI3K/AKT pathway, which may have clinical implications for overcoming

Language: Английский

Citations

0