Evidence map›Paper›PMID 40711656›Full record

ArticleInternational journal of clinical oncology2025

The Metazoan SpoT Homolog 1 promotes ferroptosis by regulating the intracellular redox cycle and iron levels in hepatocellular carcinoma.

Yuki Nakayama, Shinji Itoh, Takeo Toshima, Kyohei Yugawa, Shohei Yoshiya, Norifumi Iseda, Yuriko Tsutsui, Katsuya Toshida, Takuma Ishikawa, Tomoharu Yoshizumi

Abstract read
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Article in International journal of clinical oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Identification of 4,5,6,7-Tetrabromo-1bioRxiv : the preprint server for biology · 2026
    Article
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

10 authors.

Yuki NakayamaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Fukuoka, 812-8582, Japan.
Shinji ItohDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Fukuoka, 812-8582, Japan. itoh.shinji.453@m.kyushu-u.ac.jps.ORCID http://orcid.org/0000-0003-0382-2520
Takeo ToshimaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Fukuoka, 812-8582, Japan.
Kyohei YugawaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Fukuoka, 812-8582, Japan.
Shohei YoshiyaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Fukuoka, 812-8582, Japan.
Norifumi IsedaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Fukuoka, 812-8582, Japan.
Yuriko TsutsuiDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Fukuoka, 812-8582, Japan.
Katsuya ToshidaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Fukuoka, 812-8582, Japan.
Takuma IshikawaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Fukuoka, 812-8582, Japan.
Tomoharu YoshizumiDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Fukuoka, 812-8582, Japan.

Funding

Japan Society for the Promotion of Science London JP-19K09198Japan Society for the Promotion of Science London JP-23K08133
6 · The paper itself

Abstract

backgroundFerroptosis, a form of programmed cell death, is a potential target for cancer therapy. Metazoan SpoT Homolog 1 (MESH1) possesses intracellular NADPH phosphatase activity, which has been linked to ferroptosis. However, the molecular effects on the ferroptosis in hepatocellular carcinoma (HCC) remain unclear. This study aimed to investigate the relationship between MESH1 expression and the prognosis of patients with HCC, as well as its impact on ferroptosis in HCC cells.

methodsWe used resected specimens from patients to assess the relationship between MESH1 expression and prognosis. HCC cell lines were used to evaluate the impact of MESH1 expression on the cell phenotype and ferroptosis through various assays, RNA sequencing, and an animal experiment with xenograft mice model.

resultsWe found that high MESH1 expression correlated with good outcomes. Further investigation demonstrated that MESH1 also exhibits NADPH phosphatase activity in HCC, contributing to increased sensitivity to ferroptosis when the ferroptosis inducer was used. Similar results were observed with other ferroptosis inducers, sorafenib and lenvatinib. Notably, RNA sequencing analysis of cells with MESH1 KD revealed a correlation between intracellular iron homeostasis and MESH1 levels. These results suggested that MESH1 also can affect ferroptosis sensitivity through changing intracellular iron levels. Tumors derived from MESH1 KD cells in xenograft mice showed reduced sensitivity to sorafenib and lenvatinib, further supporting the role of MESH1 ferroptosis regulation.

conclusionThis study suggests that MESH1 influences intracellular redox and iron regulatory pathways, both of which are linked to cellular processes associated with ferroptosis.

Indexed as

Carcinoma, HepatocellularFerroptosisIronLiver NeoplasmsAnimalsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMaleMiceOxidation-ReductionPhenylurea CompoundsPrognosisQuinolinesSorafenibIronlenvatinibPhenylurea CompoundsQuinolinesSorafenibFerroptosisHepatocellular carcinomaIron homeostasisMetazoan SpoT Homolog 1Redox cycle

Identifiers

PMID40711656

What Socratic holds

Textmetadata
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 Socratic graph.