METTL3/16-mediated m6A modification of ZNNT1 promotes hepatocellular carcinoma progression by activating ZNNT1/osteopontin/S100A9 positive feedback loop-mediated crosstalk between macrophages and tumour cells

METTL3/16-mediated m6A modification of ZNNT1 promotes hepatocellular carcinoma progression by activating ZNNT1/osteopontin/S100A9 positive feedback loop-mediated crosstalk between macrophages and tumour cells

Copyright © 2024 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 261(2024) vom: 11. Apr., Seite 109924
1. Verfasser: Wei, Huamei (VerfasserIn)
Weitere Verfasser: Li, Wenchuan, Yang, Meng, Fang, Quan, Nian, Jiahui, Huang, Youguan, Wei, Qing, Huang, Zihua, Liu, Guoman, Xu, Zuoming, Hu, Anbin, Pu, Jian
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Crosstalk Hepatocellular carcinoma N(6)-methyladenosine Positive feedback loop Tumour-associated macrophage Osteopontin 106441-73-0 METTL3 protein, human mehr... EC 2.1.1.62 Methyltransferases EC 2.1.1.- METTL16 protein, human
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100 1 |a Wei, Huamei  |e verfasserin  |4 aut 
245 1 0 |a METTL3/16-mediated m6A modification of ZNNT1 promotes hepatocellular carcinoma progression by activating ZNNT1/osteopontin/S100A9 positive feedback loop-mediated crosstalk between macrophages and tumour cells 
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520 |a Macrophages are the major components of tumour microenvironment, which play critical roles in tumour development. N6-methyladenosine (m6A) also contributes to tumour progression. However, the potential roles of m6A in modulating macrophages in hepatocellular carcinoma (HCC) are poorly understood. Here, we identified ZNNT1 as an HCC-related m6A modification target, which was upregulated and associated with poor prognosis of HCC. METTL3 and METTL16-mediated m6A modification contributed to ZNNT1 upregulation through stabilizing ZNNT1 transcript. ZNNT1 exerted oncogenic roles in HCC. Furthermore, ZNNT1 recruited and induced M2 polarization of macrophages via up-regulating osteopontin (OPN) expression and secretion. M2 Macrophages-recruited by ZNNT1-overexpressed HCC cells secreted S100A9, which further upregulated ZNNT1 expression in HCC cells via AGER/NF-κB signaling. Thus, this study demonstrates that m6A modification activated the ZNNT1/OPN/S100A9 positive feedback loop, which promoted macrophages recruitment and M2 polarization, and enhanced malignant features of HCC cells. m6A modification-triggered ZNNT1/OPN/S100A9 feedback loop represents potential therapeutic target for HCC 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a Crosstalk 
650 4 |a Hepatocellular carcinoma 
650 4 |a N(6)-methyladenosine 
650 4 |a Positive feedback loop 
650 4 |a Tumour-associated macrophage 
650 7 |a Osteopontin  |2 NLM 
650 7 |a 106441-73-0  |2 NLM 
650 7 |a METTL3 protein, human  |2 NLM 
650 7 |a EC 2.1.1.62  |2 NLM 
650 7 |a Methyltransferases  |2 NLM 
650 7 |a EC 2.1.1.-  |2 NLM 
650 7 |a METTL16 protein, human  |2 NLM 
650 7 |a EC 2.1.1.-  |2 NLM 
700 1 |a Li, Wenchuan  |e verfasserin  |4 aut 
700 1 |a Yang, Meng  |e verfasserin  |4 aut 
700 1 |a Fang, Quan  |e verfasserin  |4 aut 
700 1 |a Nian, Jiahui  |e verfasserin  |4 aut 
700 1 |a Huang, Youguan  |e verfasserin  |4 aut 
700 1 |a Wei, Qing  |e verfasserin  |4 aut 
700 1 |a Huang, Zihua  |e verfasserin  |4 aut 
700 1 |a Liu, Guoman  |e verfasserin  |4 aut 
700 1 |a Xu, Zuoming  |e verfasserin  |4 aut 
700 1 |a Hu, Anbin  |e verfasserin  |4 aut 
700 1 |a Pu, Jian  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Clinical immunology (Orlando, Fla.)  |d 1999  |g 261(2024) vom: 11. Apr., Seite 109924  |w (DE-627)NLM098196855  |x 1521-7035  |7 nnns 
773 1 8 |g volume:261  |g year:2024  |g day:11  |g month:04  |g pages:109924 
856 4 0 |u http://dx.doi.org/10.1016/j.clim.2024.109924  |3 Volltext 
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