Evidence map›Paper›PMID 40604925›Full record

ArticleCancer cell international2025

GADD45GIP1 promotes osteosarcoma progression by modulating RPL35 ubiquitination and alleviating endoplasmic reticulum stress via the PERK/eIF2α pathway.

Zhiqiang Li, Xiao Yu, Renjie Xu, Xiangxin Zhang, Jun Shen, Wei Xu

Abstract read
In one paragraph

Article in Cancer cell international, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

6 authors.

Zhiqiang Li *Department of Orthopaedics Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, China.
Xiao Yu *Department of Orthopaedics Surgery, Suzhou Municipal Hospital, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Nanjing Medical University, Suzhou, 215002, China.
Renjie XuDepartment of Orthopaedics Surgery, Suzhou Municipal Hospital, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Nanjing Medical University, Suzhou, 215002, China.
Xiangxin ZhangDepartment of Orthopaedics Surgery, Suzhou Municipal Hospital, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Nanjing Medical University, Suzhou, 215002, China.
Jun ShenDepartment of Orthopaedics Surgery, Suzhou Municipal Hospital, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Nanjing Medical University, Suzhou, 215002, China. sj@njmu.edu.cn.
Wei XuDepartment of Orthopaedics Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, China. 13962157016@139.com.

Funding

Key R&D Program of Jiangsu Province BE2021659Science and Technology Development Program of Suzhou SLJ2021020Science and Technology Development Program of Suzhou SLJ2022014Youth Backbone Research Cultivation Program of Gusu School of Nanjing Medical University GSKY20220521
6 · The paper itself

Abstract

Osteosarcoma, a common and aggressive bone tumor found in adolescents and children, is associated with a poor prognosis. The investigation of new molecular mechanisms is deemed vital for the development of innovative treatments. Transcriptomic survival analysis and single-cell RNA sequencing have identified seven highly expressed genes, including GADD45G interacting protein 1 (GADD45GIP1), that are linked to poor prognosis in patients with osteosarcoma. Tissue arrays, comprising 41 normal and 67 tumor cases, have further confirmed the high expression of GADD45GIP1 in osteosarcoma. Functional tests have demonstrated that the silencing of GADD45GIP1 significantly reduces the migration and proliferation of osteosarcoma cells in vitro and in vivo, while its overexpression has the opposite effect. Mechanistic studies have revealed 263 proteins that potentially interact with GADD45GIP1, identified through immunoprecipitation (IP) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), with RPL35 ranking second among them. Cellular interference with RPL35 has been shown to activate the PERK-eIF2α pathway, increase endoplasmic reticulum (ER) stress, and affect the biological behavior of tumor cells. Additionally, the knockdown of GADD45GIP1 has led to a decrease in RPL35 protein stability and elevated polyubiquitination. Notably, the overexpression of RPL35 has counteracted the decrease in cell vitality induced by GADD45GIP1 knockdown. Thus, the high expression of GADD45GIP1 in osteosarcoma has been shown to inhibit the ubiquitin-mediated degradation of RPL35 and induce ER stress through the activation of the PERK-eIF2α pathway, thereby promoting the progression of osteosarcoma. This indicates that GADD45GIP1 serves as a key driver in the development of osteosarcoma and is a potential target for the prevention and therapy of osteosarcoma.

Indexed as

GADD45GIP1OsteosarcomaRPL35Ubiquitination

Identifiers

PMID40604925
PMCPMC12220624

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.