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

NAT10 mediated ac4C acetylation driven m6A modification via involvement of YTHDC1-LDHA/PFKM regulates glycolysis and promotes osteosarcoma DOI Creative Commons

Zhongting Mei,

Zhihua Shen,

Jiaying Pu

et al.

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

Published: Jan. 17, 2024

Abstract The dynamic changes of RNA N6-methyladenosine (m 6 A) during cancer progression participate in various cellular processes. However, less is known about a possible direct connection between upstream regulator and m A modification, therefore affects oncogenic progression. Here, we have identified that key enzyme N4-acetylcytidine (ac4C) acetylation NAT10 highly expressed human osteosarcoma tissues, its knockdown enhanced contents significantly suppressed cell growth, migration invasion. Further results revealed silence inhibits mRNA stability translation reader protein YTHDC1, displayed an increase glucose uptake, decrease lactate production pyruvate content. YTHDC1 recognizes differential sites on enzymes glycolysis phosphofructokinase (PFKM) dehydrogenase (LDHA) mRNAs, which suppress pathway by increasing them methylation-dependent manner. partially abrogated the inhibitory effect caused tumor models vivo, lentiviral overexpression restored reduced depleting at level. Altogether, found ac4C driven modification can positively regulate cells reveals previously unrecognized signaling axis NAT10/ac4C-YTHDC1/m A-LDHA/PFKM osteosarcoma.

Language: Английский

Citations

13
NAT10-mediated upregulation of GAS5 facilitates immune cell infiltration in non-small cell lung cancer via the MYBBP1A-p53/IRF1/type I interferon signaling axis DOI Creative Commons
Zimu Wang, Jing Luo, Hairong Huang

et al.

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

Published: May 18, 2024

Abstract Interactions of tumor cells with immune in the microenvironment play an important role during malignancy progression. We previously identified that GAS5 inhibited development by suppressing proliferation non-small cell lung cancer (NSCLC). Herein, we discovered a tumor-suppressing for cell-derived regulating microenvironment. positively coordinated infiltration macrophages and T NSCLC clinically, overexpression promoted recruitment both vitro vivo. Mechanistically, stabilized p53 directly binding to MYBBP1A facilitating MYBBP1A-p53 interaction, enhanced p53-mediated transcription IRF1, which activated type I interferon signaling increased production downstream CXCL10 CCL5. also found activation was associated better immunotherapy efficacy NSCLC. Furthermore, stability regulated NAT10, key enzyme responsible N4-acetylcytidine (ac4C) modification, bound mediated its ac4C modification. Collectively, could activate via MYBBP1A-p53/IRF1 axis, promoting potentially correlating efficacy, suppressed Our results suggested as promising predictive marker potential therapeutic target combination therapy

Language: Английский

Citations

11
The role of tumor-derived exosomal LncRNA in tumor metastasis DOI

Zhongren Yu,

Jiali Fu, Vanya Mantareva

et al.

Cancer Gene Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Language: Английский

Citations

1
NAT10 promotes the progression of clear cell renal cell carcinoma by regulating ac4C acetylation of NFE2L3 and activating AKT/GSK3β signaling pathway DOI Creative Commons

Zenghui Sun,

Yuqiong Wang, Chao Zheng

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 2, 2025

Clear cell renal carcinoma (ccRCC) is the most common histological subtype of carcinoma, and tumour growth metastasis ccRCC are related to prognosis. N4-acetylcytidine (ac4C) one major modifications RNA known be mediated by N-acetyltransferase 10 (NAT10). The role NAT10 in cancer gradually being revealed, although NAT10-mediated ac4C modification has not been reported. In this study, was found upregulated tissues associated with a poor prognosis patients. HIF-1α activated expression at transcriptional level. CCK8, EdU, Transwell scratch assays after knockdown or overexpression showed that promoted proliferation migration. results subcutaneous xenograft caudal vein injection vivo, while Remodelin inhibited growth. acRIP-seq, RIP, stability dual luciferase reporter experiments acetylation NFE2L3 mRNA stability. ChIP-seq regulated LASP1 thus AKT/GSK3β signalling pathway. summary, our suggest mediates mRNA, promotes its stability, regulates LASP1-AKT/GSK3β/β-catenin axis progression clear carcinoma.

Language: Английский

Citations

1
NAT10-mediated RNA acetylation enhances HNRNPUL1 mRNA stability to contribute cervical cancer progression DOI Creative Commons

Yingfei Long,

Yifei Ren,

Qinglv Wei

et al.

International Journal of Medical Sciences, Journal Year: 2023, Volume and Issue: 20(8), P. 1079 - 1090

Published: Jan. 1, 2023

N4-acetylcytidine (ac4C) is a lately discovered nucleotide modification that has been shown to be closely implicated in cancer.N-acetyltransferase10(NAT10) acts as an enzyme regulates mRNA acetylation modifications.Currently, the role of NAT10-mediated RNA cervical cancer remains elucidated.On basis transcriptome analysis TCGA and GEO open datasets (GSE52904, GSE29570, GSE122697), NAT10 upregulated tissues correlated with poor prognosis.Knockdown suppressed cell proliferation, invasion, migration cells.The vivo oncogenic function was also confirmed xenograft models.Combined RNA-seq acRIP-seq revealed HNRNPUL1 target cancer.NAT10 positively regulate expression by promoting ac4C stability mRNA.Furthermore, depletion division, cancer.HNRNPUL1 overexpression partially restored cellular cells knockdown.Thus, this study demonstrates contributes progression enhancing via modification, NAT10-ac4C-HNRNPUL1 axis might potential for therapy.

Language: Английский

Citations

22
N4-acetylcytidine-dependent GLMP mRNA stabilization by NAT10 promotes head and neck squamous cell carcinoma metastasis and remodels tumor microenvironment through MAPK/ERK signaling pathway DOI Creative Commons
Yuanyuan Liu, Xing Wang, Yuying Liu

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(11)

Published: Nov. 1, 2023

Abstract N4-acetylcytidine (ac4C) is a post-transcriptional RNA modification that regulates in various important biological processes. However, its role human cancer, especially lymph node metastasis, remains largely unknown. Here, we demonstrated N-Acetyltransferase 10 (NAT10), as the only known “writer” of ac4C mRNA modification, was highly expressed head and neck squamous cell carcinoma (HNSCC) patients with metastasis. High NAT10 levels nodes HNSCC are predictor poor overall survival. Moreover, found high expression positively upregulated by Nuclear Respiratory Factor 1 (NRF1) transcription factor. Gain- loss-of-function experiments displayed promoted metastasis mice. Mechanistically, induced Glycosylated Lysosomal Membrane Protein (GLMP) stabilized mRNA, which triggered activation MAPK/ERK signaling pathway. Finally, NAT10-specific inhibitor, remodelin, could inhibit tumorigenesis 4-Nitroquinoline 1-oxide (4NQO)-induced murine tumor model remodel microenvironment, including angiogenesis, CD8 + T cells Treg recruitment. These results demonstrate promotes via ac4C-dependent stabilization GLMP transcript, providing potential epitranscriptomic-targeted therapeutic strategy for HNSCC.

Language: Английский

Citations

21
Autophagic blockade potentiates anlotinib-mediated ferroptosis in anaplastic thyroid cancer DOI Creative Commons
Jiajun Wu, Juyong Liang, Ruiqi Liu

et al.

Endocrine Related Cancer, Journal Year: 2023, Volume and Issue: 30(9)

Published: June 7, 2023

Anlotinib-mediated angiogenic remodeling was delineated in various tumors. Meanwhile, we previously showed that anlotinib inhibited tumor angiogenesis anaplastic thyroid cancer (ATC). However, the potential role of on cell lethality ATC remains an enigma. Herein, found viability, proliferation, and migration KHM-5M, C643, 8505C cells a dose-dependently manner. Under treatment, PANoptosis (pyroptosis, apoptosis, necroptosis) markers were not changed; however, ferroptosis targets (transferrin, HO-1, FTH1, FTL, GPX4) significantly downregulated. ROS levels also increased concentration-dependent manner after treatment cells. In addition, protective autophagy activated response to anlotinib, autophagic blockade potentiated anlotinib-mediated antitumor effects vitro vivo . Our new discovery identified autophagy-ferroptosis signaling pathway which provides mechanistic insight into death, synergistic combination therapy may help develop strategies.

Language: Английский

Citations

18
Exosomal lncRNA Mir100hg derived from cancer stem cells enhance glycolysis and promote metastasis of lung adenocarcinoma through mircroRNA-15a-5p/31-5p DOI Creative Commons
Lei Shi, Bowen Li, Yuhan Zhang

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Sept. 21, 2023

Abstract Background Exosomes are a new class of molecular entities in the metastatic microenvironment, which can mediate bidirectional communication between cells. While exosomes-mediated interactions tumor cells and other cell populations microenvironment have attracted most attention, little is known about significance exosomes mediating interaction non-stemness cancer stem during progression. Methods The structure, sequence downstream target miRNAs lncRNA Mir100hg were predicted by online web resources. bioinformatics prediction results validated with experimental verification: exosome tracing, electron microscopy, Luciferase assay, metabolomics sequencing mouse tail vein model pulmonary metastasis. A complex regulatory network "cancer cells-exosomal lncRNA-non-stem cells" was constructed. Results This study demonstrates firstly that upregulated lung LLC-SD (Lung cells) be delivered to LLC (Lewis via exosomes. In LLC, targets miR-15a-5p miR-31-5p leads increase global glycolytic activity consequently, enhancement their capability. Conclusion We delineated utilized transfer high low-metastatic through exosomal Mir100hg, thereby providing mechanistic insights into two heterogeneous

Language: Английский

Citations

18
The emerging roles of ac4C acetylation “writer” NAT10 in tumorigenesis: A comprehensive review DOI
Leisheng Wang, Tao Yue, Jingbo Zhai

et al.

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 254, P. 127789 - 127789

Published: Nov. 4, 2023

Language: Английский

Citations

17
Recent advances in the potential role of RNA N4-acetylcytidine in cancer progression DOI Creative Commons
Shujun Zhang, Yafeng Liu, Xiao Ma

et al.

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

Published: Jan. 17, 2024

Abstract N 4 -acetylcytidine (ac C) is a highly conserved chemical modification widely found in eukaryotic and prokaryotic RNA, such as tRNA, rRNA, mRNA. This significantly associated with various human diseases, especially cancer, its formation depends on the catalytic activity of N-acetyltransferase 10 (NAT10), only known protein that produces ac C. review discusses detection techniques regulatory mechanisms C summarizes correlation tumor occurrence, development, prognosis, drug therapy. It also comments new biomarker for early diagnosis prognosis prediction target

Language: Английский

Citations

8