Publication Name	World Journal of Gastroenterology
Manuscript ID	118472
Country	China

Category	Oncology
Manuscript Type	Basic Study
Article Title	H3K18 La-METTL5-CCT2 signaling axis promotes colorectal cancer progression by inhibiting pyroptosis
Manuscript Source	Unsolicited Manuscript
All Author List	Xiao-Peng Wang, Chang Liu, Hao-Wen Zhang, Jing-Ming Zhai, Jia-Xin Zhu, Guan-Duo Sun, Ya-Hang An, Hai-Jun Yang, Dong-Shuai Jing and De-Chun Liu
Funding Agency and Grant Number	Funding Agency Grant Number Henan Province Science and Technology Research Project 232102310043 Henan Provincial Science and Technology Research and Development Plan Joint Fund Project 222103810047 Key Scientific Research Project Plan of Colleges and Universities in Henan Province 22A320033
Corresponding Author	De-Chun Liu, PhD, Department of Gastrointestinal Surgery, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, No. 24 Jinghua Road, Jianxi District, Luoyang 471003, Henan Province, China. lydocliu666@163.com
Key Words	Colorectal cancer; Histone lactylation; H3K18 La; METTL5; CCT2; Pyroptosis; M6A methylation; Lactate
Core Tip	Lactate-induced histone H3K18 lactylation drives colorectal cancer progression by activating METTL5 transcription. METTL5 stabilizes CCT2 mRNA via m6A modification, upregulating CCT2 expression and inhibiting pyroptosis. This H3K18 lactylation-METTL5-CCT2 signaling axis links metabolic reprogramming, epigenetics, and RNA methylation to suppress cell death and promote malignancy. Targeting this pathway with the PI3Kβ inhibitor AZD6482 increases oxaliplatin cytotoxicity in high-lactate microenvironments, offering a novel therapeutic strategy for colorectal cancer.
Citation	Wang XP, Liu C, Zhang HW, Zhai JM, Zhu JX, Sun GD, An YH, Yang HJ, Jing DS, Liu DC. H3K18 La-METTL5-CCT2 signaling axis promotes colorectal cancer progression by inhibiting pyroptosis. World J Gastroenterol 2026; In press

Received	2026-01-04 07:43
Peer-Review Started	2026-01-04 07:44
First Decision by Editorial Office Director	2026-01-26 09:08
Return for Revision	2026-01-26 09:08
Revised	2026-03-31 11:14
Publication Fee Transferred
Second Decision by Editor	2026-05-25 02:37
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-05-25 09:49
Articles in Press	2026-05-25 09:49
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1007-9327 (print) and 2219-2840 (online)
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