Evidence map›Paper›PMID 40133552›Full record

ArticleScientific reports2025

NELL2 suppresses epithelial-mesenchymal transition and induces ferroptosis via notch signaling pathway in HCC.

Shiqi Liu, Haomin Wu, Pengjie Zhang, Haonan Zhou, Di Wu, Yifan Jin, Hongwei Yang, Ruilin Xing, Yubo Wu, Gang Wu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–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

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. 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

10 authors.

Shiqi Liu *Hepatobiliary Surgery Department, First Hospital of China Medical University, No.155, Nanjingbei Street, Shenyang, 110001, Liaoning, People's Republic of China.
Haomin Wu *Hepatobiliary Surgery Department, First Hospital of China Medical University, No.155, Nanjingbei Street, Shenyang, 110001, Liaoning, People's Republic of China.
Pengjie ZhangHepatobiliary Surgery Department, First Hospital of China Medical University, No.155, Nanjingbei Street, Shenyang, 110001, Liaoning, People's Republic of China.
Haonan ZhouHepatobiliary Surgery Department, First Hospital of China Medical University, No.155, Nanjingbei Street, Shenyang, 110001, Liaoning, People's Republic of China.
Di WuHepatobiliary Surgery Department, First Hospital of China Medical University, No.155, Nanjingbei Street, Shenyang, 110001, Liaoning, People's Republic of China.
Yifan JinHepatobiliary Surgery Department, First Hospital of China Medical University, No.155, Nanjingbei Street, Shenyang, 110001, Liaoning, People's Republic of China.
Hongwei YangHepatobiliary Surgery Department, First Hospital of China Medical University, No.155, Nanjingbei Street, Shenyang, 110001, Liaoning, People's Republic of China.
Ruilin XingHepatobiliary Surgery Department, First Hospital of China Medical University, No.155, Nanjingbei Street, Shenyang, 110001, Liaoning, People's Republic of China.
Yubo WuHepatobiliary Surgery Department, First Hospital of China Medical University, No.155, Nanjingbei Street, Shenyang, 110001, Liaoning, People's Republic of China.
Gang WuHepatobiliary Surgery Department, First Hospital of China Medical University, No.155, Nanjingbei Street, Shenyang, 110001, Liaoning, People's Republic of China. cmuwgzwl@126.com.

Funding

Central guidance for local scientific and technological development project 2023JH6/100100014Major Science and Technology Special Project in Liaoning Province 2019JH1/10300007
6 · The paper itself

Abstract

Although various malignant tumors have been associated with the aberrant expression of Neural Epidermal Growth Factor-Like 2 (NELL2), its involvement in hepatocellular carcinoma (HCC) has not been previously documented. In this study, NELL2, recognized as a crucial tumor-suppressor gene, was found to be infrequently expressed in HCC. In vitro experiments demonstrated that the overexpression of NELL2 significantly inhibited the proliferation, migration, and invasion of liver cancer cells, whereas the suppression of NELL2 markedly enhanced these oncogenic properties. Further investigation revealed that NELL2 impedes epithelial-mesenchymal transition (EMT) via the Notch signaling pathway. Inhibition of the Notch pathway reversed the increased tumor proliferation, migration, and invasion observed following the downregulation of NELL2 expression. Notably, gene enrichment analysis and in vitro studies indicated that NELL2 effectively induced ferroptosis in HCC cells, as evidenced by increased levels of cellular malondialdehyde (MDA), iron, and Reactive Oxygen Species (ROS), alongside decreased glutathione (GSH) levels. The blockade of the Notch signaling pathway substantially diminished NELL2's capacity to induce ferroptosis. In summary, our findings suggest that NELL2 modulates the Notch signaling pathway to inhibit EMT and promote ferroptosis. Consequently, NELL2 may serve as a novel therapeutic target, potentially functioning as a tumor suppressor gene in HCC.

Indexed as

Calcium-Binding ProteinsCarcinoma, HepatocellularEpithelial-Mesenchymal TransitionFerroptosisLiver NeoplasmsNerve Tissue ProteinsReceptors, NotchSignal TransductionCell Line, TumorCell MovementCell ProliferationGene Expression Regulation, NeoplasticHumansCalcium-Binding ProteinsNerve Tissue ProteinsReceptors, NotchEMTFerroptosisHCCNELL2Notch pathway

Identifiers

PMID40133552
PMCPMC11937300

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.