Evidence map›Paper›PMID 35522946›Full record

ArticleClinical and translational medicine2022

The N6-methyladenosine modification enhances ferroptosis resistance through inhibiting SLC7A11 mRNA deadenylation in hepatoblastoma.

Li Liu, Jiangtu He, Guifeng Sun, Nan Huang, Zhixuan Bian, Chang Xu, Yue Zhang, Zhongqi Cui, Wenqiang Xu, Fenyong Sun and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
116citing papers in PubMed, 2 pooled it
11.8field-weighted citation impact, top 1% of its field
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

116 citing papers in PubMed, 2 syntheses or guidelines pooled it, 140 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. The emerging roles of disulfidptosis in cancer.Apoptosis : an international journal on programmed cell death · 2026
    Review
  4. ER-Localized DeadenylaseExploration (Beijing, China) · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. RNA modifications and cancer ferroptosis.Cancer cell international · 2026
    Review
  19. Review
  20. Review

56 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Commented on by
    N2022
5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Li LiuDepartment of Clinical Laboratory, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.ORCID 0000-0002-7047-7977
Jiangtu HeDepartment of Clinical Laboratory, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Guifeng SunDepartment of Clinical Laboratory, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Nan HuangDepartment of Clinical Laboratory, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Zhixuan BianDepartment of Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Chang XuDepartment of Clinical Laboratory, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Yue ZhangDepartment of Central Laboratory, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Zhongqi CuiDepartment of Clinical Laboratory, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Wenqiang XuDepartment of Clinical Laboratory, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Fenyong SunDepartment of Clinical Laboratory, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Chengle ZhuangColorectal Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Qiuhong ManDepartment of Clinical Laboratory, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Song GuDepartment of Surgery, Shanghai Children's Medical Center, School of medicine, Shanghai Jiaotong University, Shanghai, China.
Tongji University · CNShanghai Children's Medical Center · CNShanghai Jiao Tong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSolute carrier family 7 member 11 (SLC7A11) is overexpressed in multiple human tumours and functions as a transporter importing cystine for glutathione biosynthesis. It promotes tumour development in part by suppressing ferroptosis, a newly identified form of cell death that plays a pivotal role in the suppression of tumorigenesis. However, the role and underlying mechanisms of SLC7A11-mediated ferroptosis in hepatoblastoma (HB) remain largely unknown.

methodsReverse transcription quantitative real-time PCR (RT-qPCR) and western blotting were used to measure SLC7A11 levels. Cell proliferation, colony formation, lipid reactive oxygen species (ROS), MDA concentration, 4-HNE, GSH/GSSG ratio and cell death assays as well as subcutaneous xenograft experiments were used to elucidate the effects of SLC7A11 in HB cell proliferation and ferroptosis. Furthermore, MeRIP-qPCR, dual luciferase reporter, RNA pulldown, RNA immunoprecipitation (RIP) and RACE-PAT assays were performed to elucidate the underlying mechanism through which SLC7A11 was regulated by the m6A modification in HB.

resultsSLC7A11 expression was highly upregulated in HB. SLC7A11 upregulation promoted HB cell proliferation in vitro and in vivo, inhibiting HB cell ferroptosis. Mechanistically, SLC7A11 mRNA exhibited abnormal METTL3-mediated m6A modification, which enhanced its stability and expression. IGF2 mRNA-binding protein 1 (IGF2BP1) was identified as the m6A reader of SLC7A11, enhancing SLC7A11 mRNA stability and expression by inhibiting SLC7A11 mRNA deadenylation in an m6A-dependent manner. Moreover, IGF2BP1 was found to block BTG2/CCR4-NOT complex recruitment via competitively binding to PABPC1, thereby suppressing SLC7A11 mRNA deadenylation.

conclusionsOur findings demonstrated that the METTL3-mediated SLC7A11 m6A modification enhances HB ferroptosis resistance. The METTL3/IGF2BP1/m6A modification promotes SLC7A11 mRNA stability and upregulates its expression by inhibiting the deadenylation process. Our study highlights a critical role of the m6A modification in SLC7A11-mediated ferroptosis, providing a potential strategy for HB therapy through blockade of the m6A-SLC7A11 axis.

Indexed as

Amino Acid Transport System y+FerroptosisHepatoblastomaImmediate-Early ProteinsLiver NeoplasmsAdenosineAnimalsHumansMethyltransferasesRNA, MessengerTumor Suppressor ProteinsAdenosineAmino Acid Transport System y+BTG2 protein, humanImmediate-Early ProteinsMethyltransferasesMETTL3 protein, humanN-methyladenosineRNA, MessengerSLC7A11 protein, humanTumor Suppressor ProteinsferroptosishepatoblastomaIGF2BP1m6A methylationresistanceSLC7A11

Identifiers

PMID35522946
PMCPMC9076012
OpenAlexW4229077545

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.