Evidence mapPaperPMID 41845506Full record

ArticleJournal of experimental & clinical cancer research : CR2026

METTL16-mediated m

Yongheng Zhao, Tingyue Gong, Hao Li, Haiping Lin, Minhao Yu, Yang Luo, Ming Zhong, Jun Qin

Abstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Yongheng Zhao *Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Tingyue Gong *Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hao Li *Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Haiping LinDepartment of General Surgery, Jinhua Central Hospital, Teaching Hospital of Mathematical Medicine College, Zhejiang Normal University, Zhejiang, China.
Minhao YuDepartment of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yang LuoDepartment of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. lykshuiyang@163.com.
Ming ZhongDepartment of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. drzhongming1966@163.com.
Jun QinDepartment of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. qinjun@renji.com.

Funding

National Natural Science Foundation of China 81873555Shanghai Pudong New District Science and Technology Innovation Project PKJ2025-Y18Shanghai Shenkang Clinical Development Center SHDC2020CR5006
6 · The paper itself

Abstract

backgroundN6-methyladenosine (m6A) is the most abundant post-transcriptional modification, and METTL16 has recently emerged as a pivotal m6A methyltransferase in cancer. Cholesterol metabolic reprogramming and aberrant MAPK signaling sustain the malignant initiation and progression of colorectal cancer (CRC). However, whether - and how - m6A regulation, particularly by METTL16, interfaces with cholesterol metabolism and downstream oncogenic signaling in CRC remains unknown.

methodsDifferential expression of METTL16 in CRC was identified through bioinformatic analyses and validated by qRT-PCR, immunoblotting, and immunohistochemistry (IHC). The functional role of METTL16 in CRC progression was examined using in vitro assays and xenograft models. To identify downstream targets, RNA-seq and MeRIP-seq were performed, revealing MSMO1 as a METTL16-regulated gene. The mechanistic basis of the METTL16–MSMO1 axis was investigated through immunoprecipitation-Mass Spectrometry (IP-MS), co-immunoprecipitation (Co-IP), RNA immunoprecipitation (RIP), MeRIP-qPCR, and RNA stability assays. Cholesterol metabolism analyses were conducted to further characterize the metabolic consequences of METTL16–MSMO1 regulation.

resultsMETTL16 was significantly upregulated in CRC and correlated with poor clinical outcomes. Mechanistically, METTL16 enhanced m6A modification of MSMO1, stabilizing its transcript via IGF2BP2 and disrupting intracellular cholesterol homeostasis, which triggered ER stress and activated MAPK-p38/ NF-κB signaling by promoting TAK1/TAB complex formation and TAK1 autophosphorylation, thereby driving CRC progression. Additionally, elevated cholesterol levels further reshaped global m6A methylation patterns and altered methyltransferase expression, suggesting a reciprocal feedback loop between cholesterol metabolism and epigenetic regulation.

conclusionsThese findings underscore the critical role of the METTL16–MSMO1 axis in driving cholesterol metabolic reprogramming that fuels MAPK-p38/NF-κB oncogenic signaling in CRC, highlighting promising biomarkers and therapeutic targets for improved disease management.

Indexed as

AdenosineCholesterolColorectal NeoplasmsMethyltransferasesNF-kappa Bp38 Mitogen-Activated Protein KinasesAnimalsCell Line, TumorEpitranscriptomeFemaleGene Expression Regulation, NeoplasticHumansMaleMiceRNA MethylationSignal TransductionAdenosineCholesterolMethyltransferasesMETTL16 protein, humanNF-kappa BN-methyladenosinep38 Mitogen-Activated Protein KinasescholesterolColorectal Cancer (CRC)MAPKMETTL16MSMO1N6-methyladenosine(m6A)

Identifiers

PMID41845506
PMCPMC13181995

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.