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NAT10 promotes the progression of clear cell renal cell carcinoma by regulating ac4C acetylation of NFE2L3 and activating AKT/GSK3β signaling pathway
by
Zheng, Chao
, Wang, Yuqiong
, Sun, Qiyu
, Chang, Mingjie
, Li, Wenjuan
, Sun, Zenghui
, Zang, Yuanwei
, Xiao, Lixiang
, Ren, Juchao
, Fang, Liang
, Cui, Xixi
in
13/31
/ 13/51
/ 13/95
/ 631/67/589/1588/1351
/ 631/80
/ 64/60
/ 82/80
/ Acetylation
/ Acetyltransferase
/ AKT protein
/ Animals
/ Antibodies
/ Biochemistry
/ Biomedical and Life Sciences
/ Cancer
/ Carcinoma, Renal Cell - genetics
/ Carcinoma, Renal Cell - metabolism
/ Carcinoma, Renal Cell - pathology
/ Cell Biology
/ Cell Culture
/ Cell Line, Tumor
/ Cell migration
/ Cell Movement - genetics
/ Cell proliferation
/ Cell Proliferation - genetics
/ Clear cell-type renal cell carcinoma
/ Disease Progression
/ Female
/ Gene Expression Regulation, Neoplastic
/ Glycogen Synthase Kinase 3 beta - metabolism
/ Humans
/ Hypoxia-inducible factor 1a
/ Immunology
/ Kidney cancer
/ Kidney Neoplasms - genetics
/ Kidney Neoplasms - metabolism
/ Kidney Neoplasms - pathology
/ Life Sciences
/ Male
/ Metastases
/ Metastasis
/ Mice
/ Mice, Inbred BALB C
/ Mice, Nude
/ mRNA stability
/ N-Acetyltransferase
/ N-Terminal Acetyltransferase E - genetics
/ N-Terminal Acetyltransferase E - metabolism
/ N-Terminal Acetyltransferases
/ Prognosis
/ Proto-Oncogene Proteins c-akt - metabolism
/ RNA modification
/ Signal Transduction
/ Tumors
/ β-Catenin
2025
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NAT10 promotes the progression of clear cell renal cell carcinoma by regulating ac4C acetylation of NFE2L3 and activating AKT/GSK3β signaling pathway
by
Zheng, Chao
, Wang, Yuqiong
, Sun, Qiyu
, Chang, Mingjie
, Li, Wenjuan
, Sun, Zenghui
, Zang, Yuanwei
, Xiao, Lixiang
, Ren, Juchao
, Fang, Liang
, Cui, Xixi
in
13/31
/ 13/51
/ 13/95
/ 631/67/589/1588/1351
/ 631/80
/ 64/60
/ 82/80
/ Acetylation
/ Acetyltransferase
/ AKT protein
/ Animals
/ Antibodies
/ Biochemistry
/ Biomedical and Life Sciences
/ Cancer
/ Carcinoma, Renal Cell - genetics
/ Carcinoma, Renal Cell - metabolism
/ Carcinoma, Renal Cell - pathology
/ Cell Biology
/ Cell Culture
/ Cell Line, Tumor
/ Cell migration
/ Cell Movement - genetics
/ Cell proliferation
/ Cell Proliferation - genetics
/ Clear cell-type renal cell carcinoma
/ Disease Progression
/ Female
/ Gene Expression Regulation, Neoplastic
/ Glycogen Synthase Kinase 3 beta - metabolism
/ Humans
/ Hypoxia-inducible factor 1a
/ Immunology
/ Kidney cancer
/ Kidney Neoplasms - genetics
/ Kidney Neoplasms - metabolism
/ Kidney Neoplasms - pathology
/ Life Sciences
/ Male
/ Metastases
/ Metastasis
/ Mice
/ Mice, Inbred BALB C
/ Mice, Nude
/ mRNA stability
/ N-Acetyltransferase
/ N-Terminal Acetyltransferase E - genetics
/ N-Terminal Acetyltransferase E - metabolism
/ N-Terminal Acetyltransferases
/ Prognosis
/ Proto-Oncogene Proteins c-akt - metabolism
/ RNA modification
/ Signal Transduction
/ Tumors
/ β-Catenin
2025
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NAT10 promotes the progression of clear cell renal cell carcinoma by regulating ac4C acetylation of NFE2L3 and activating AKT/GSK3β signaling pathway
by
Zheng, Chao
, Wang, Yuqiong
, Sun, Qiyu
, Chang, Mingjie
, Li, Wenjuan
, Sun, Zenghui
, Zang, Yuanwei
, Xiao, Lixiang
, Ren, Juchao
, Fang, Liang
, Cui, Xixi
in
13/31
/ 13/51
/ 13/95
/ 631/67/589/1588/1351
/ 631/80
/ 64/60
/ 82/80
/ Acetylation
/ Acetyltransferase
/ AKT protein
/ Animals
/ Antibodies
/ Biochemistry
/ Biomedical and Life Sciences
/ Cancer
/ Carcinoma, Renal Cell - genetics
/ Carcinoma, Renal Cell - metabolism
/ Carcinoma, Renal Cell - pathology
/ Cell Biology
/ Cell Culture
/ Cell Line, Tumor
/ Cell migration
/ Cell Movement - genetics
/ Cell proliferation
/ Cell Proliferation - genetics
/ Clear cell-type renal cell carcinoma
/ Disease Progression
/ Female
/ Gene Expression Regulation, Neoplastic
/ Glycogen Synthase Kinase 3 beta - metabolism
/ Humans
/ Hypoxia-inducible factor 1a
/ Immunology
/ Kidney cancer
/ Kidney Neoplasms - genetics
/ Kidney Neoplasms - metabolism
/ Kidney Neoplasms - pathology
/ Life Sciences
/ Male
/ Metastases
/ Metastasis
/ Mice
/ Mice, Inbred BALB C
/ Mice, Nude
/ mRNA stability
/ N-Acetyltransferase
/ N-Terminal Acetyltransferase E - genetics
/ N-Terminal Acetyltransferase E - metabolism
/ N-Terminal Acetyltransferases
/ Prognosis
/ Proto-Oncogene Proteins c-akt - metabolism
/ RNA modification
/ Signal Transduction
/ Tumors
/ β-Catenin
2025
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NAT10 promotes the progression of clear cell renal cell carcinoma by regulating ac4C acetylation of NFE2L3 and activating AKT/GSK3β signaling pathway
Journal Article
NAT10 promotes the progression of clear cell renal cell carcinoma by regulating ac4C acetylation of NFE2L3 and activating AKT/GSK3β signaling pathway
2025
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Overview
Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma, and the tumour growth and metastasis of ccRCC are related to prognosis. N4-acetylcytidine (ac4C) is one of the major modifications of RNA and is known to be mediated by N-acetyltransferase 10 (NAT10). The role of NAT10 in cancer is gradually being revealed, although the role of NAT10-mediated RNA ac4C modification in ccRCC has not been reported. In this study, NAT10 was found to be upregulated in ccRCC tissues and associated with a poor prognosis in patients. HIF-1α activated NAT10 expression at the transcriptional level. CCK8, EdU, Transwell and scratch assays after NAT10 knockdown or overexpression showed that NAT10 promoted cell proliferation and migration. The results of subcutaneous xenograft and caudal vein injection showed that NAT10 promoted tumour growth and metastasis in vivo, while Remodelin inhibited tumour growth. The acRIP-seq, RIP, RNA stability and dual luciferase reporter experiments showed that NAT10 activated ac4C acetylation of NFE2L3 mRNA and promoted NFE2L3 mRNA stability. The ChIP-seq results showed that NFE2L3 regulated the expression of LASP1 and thus activated the AKT/GSK3β signalling pathway. In summary, our results suggest that NAT10 mediates ac4C acetylation of NFE2L3 mRNA, promotes its mRNA stability, regulates the LASP1-AKT/GSK3β/β-catenin axis and promotes the progression of renal clear cell carcinoma.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ 13/51
/ 13/95
/ 631/80
/ 64/60
/ 82/80
/ Animals
/ Biomedical and Life Sciences
/ Cancer
/ Carcinoma, Renal Cell - genetics
/ Carcinoma, Renal Cell - metabolism
/ Carcinoma, Renal Cell - pathology
/ Cell Proliferation - genetics
/ Clear cell-type renal cell carcinoma
/ Female
/ Gene Expression Regulation, Neoplastic
/ Glycogen Synthase Kinase 3 beta - metabolism
/ Humans
/ Kidney Neoplasms - metabolism
/ Kidney Neoplasms - pathology
/ Male
/ Mice
/ N-Terminal Acetyltransferase E - genetics
/ N-Terminal Acetyltransferase E - metabolism
/ N-Terminal Acetyltransferases
/ Proto-Oncogene Proteins c-akt - metabolism
/ Tumors
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