Evidence map›Paper›PMID 40828335›Full record

ArticleJournal of molecular histology2025

The FTO-YTHDF2 axis drives immune evasion and tumor progression in hepatocellular carcinoma via m6A-dependent FLAD1 regulation.

Chen Xu, Liangjun Jiang, Xianzhou Lu, Wei Li

Abstract read
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In one paragraph

Article in Journal of molecular histology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Chen XuDepartment of Hepatobiliary Surgery, The Affiliated Nahua Hospital, Hengyang Medical School, University of South China, No. 336 Dongfeng South Road, Zhuhui District, Hengyang, 421002, Hunan Province, China.
Liangjun JiangDepartment of Gastroenterology, The Affiliated Nahua Hospital, Hengyang Medical School, University of South China, Hengyang, 421002, Hunan, China.
Xianzhou LuDepartment of Hepatobiliary Surgery, The Affiliated Nahua Hospital, Hengyang Medical School, University of South China, No. 336 Dongfeng South Road, Zhuhui District, Hengyang, 421002, Hunan Province, China.
Wei LiDepartment of Hepatobiliary Surgery, The Affiliated Nahua Hospital, Hengyang Medical School, University of South China, No. 336 Dongfeng South Road, Zhuhui District, Hengyang, 421002, Hunan Province, China. Liweiping0734@126.com.

Funding

Hengyang City Guidance Plan Project [2021] No. 51-120Hunan Provincial Health Commission Key Guidance Project 202104010743Natural Science Foundation of Hunan Province 2024JJ7465; 2024JJ7461
6 · The paper itself

Abstract

This study investigates the molecular mechanism by which the FTO-YTHDF2 axis regulates FLAD1 expression through m6A modification to drive immune evasion and tumor progression in hepatocellular carcinoma (HCC). By bioinformatics analysis of TCGA-HCC data, FLAD1 was identified as a key oncogenic driver, with elevated expression in HCC tissues and cells. Functional experiments revealed that FLAD1 knockdown suppressed HCC proliferation, migration, invasion, and PD-L1 expression while enhancing CD8 + T cell cytotoxicity (evidenced by increased IFN-γ, TNF-α, and LDH release). Mechanistically, FTO, an m6A demethylase, upregulated FLAD1 by removing m6A marks to counteract YTHDF2-mediated mRNA degradation. In vivo, FTO silencing reduced tumor growth and PD-L1 levels while elevating pro-inflammatory cytokines, and the effects negated by YTHDF2 knockdown. These findings establish that the FTO-YTHDF2 axis promotes HCC immune evasion and tumor progression via m6A-dependent FLAD1 stabilization, highlighting the axis as a therapeutic target to disrupt tumorigenesis and restore anti-tumor immunity.

Indexed as

AdenosineAlpha-Ketoglutarate-Dependent Dioxygenase FTOCarcinoma, HepatocellularLiver NeoplasmsRNA-Binding ProteinsAnimalsCell Line, TumorCell ProliferationDisease ProgressionGene Expression Regulation, NeoplasticHumansMiceAdenosineAlpha-Ketoglutarate-Dependent Dioxygenase FTOFTO protein, humanRNA-Binding ProteinsYTHDF2 protein, humanFLAD1FTO-YTHDF2 axisHepatocellular carcinomaImmune evasion and tumor progressionm6A modification

Identifiers

PMID40828335

What OpenQuestion holds

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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 OpenQuestion graph.