Evidence map›Paper›PMID 40646517›Full record

ArticleJournal of experimental & clinical cancer research : CR2025

WDR3 undergoes phase separation to mediate the therapeutic mechanism of Nilotinib against osteosarcoma.

Minglei Li, Nan Li, Yuying Fan, Zhan Zhang, Long Zhou, Yifan Yu, Man Ni, Mingzi Tan, WanJie Huang, Tong Zhu

Abstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 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. Article
  2. Review
  3. 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.

Minglei Li *Department of Pediatric Orthopaedics, Shengjing Hospital of China Medical University, No. 36 Sanhao Street of Heping District, Shenyang, Liaoning, 110004, China.
Nan Li *Department of Pediatrics, The Fourth Afflicted Hospital of China Medical University, Shenyang, Liaoning, 110032, China.
Yuying Fan *Department of Pediatrics, Shengjing Hospital of China Medical University, No. 36 Sanhao Street of Heping District, Shenyang, Liaoning, 110004, China.
Zhan ZhangDepartment of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China.
Long ZhouDepartment of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China.
Yifan YuDepartment of General Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, China.
Man NiCollege of Veterinary Medicine, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, Jiangsu, China.
Mingzi TanDepartment of Gynecology, Liaoning Cancer Hospital & Istitute, No.44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning, 110042, China. kitefly1102@126.com.
WanJie HuangDepartment of Pediatrics, Shengjing Hospital of China Medical University, No. 36 Sanhao Street of Heping District, Shenyang, Liaoning, 110004, China. wjhuang@cmu.edu.cn.
Tong ZhuDepartment of Pediatric Orthopaedics, Shengjing Hospital of China Medical University, No. 36 Sanhao Street of Heping District, Shenyang, Liaoning, 110004, China. zhutong19860413@163.com.

Funding

Shengjing Hospital of China Medical University Intra-Hospital Program M0140
6 · The paper itself

Abstract

backgroundOsteosarcoma is highly invasive with a poor prognosis. The phenomenon of liquid-liquid phase separation (LLPS) can promote the formation of biomolecules and participate in the tumor regulation mechanism. Therefore, mining prognostic markers related to LLPS could allow patients to benefit from targeted therapies.

methodMicroarray analysis was performed to identify LLPS-related biomarkers, followed by the validation of binding interactions between genes and drugs via molecular docking analysis. Functions of key genes were investigated in U2-OS cells and xenograft mice. LLPS of WDR3 were observed by the droplet formation assay and fluorescence recovery after photobleaching. The intrinsically disordered region (IDR) of WDR3 was mutated to disrupt LLPS, which was then rescued by the fusion of hnRNAP1 IDR. Therapeutic mechanism of Nilotinib mediated by LLPS was explored in vitro and in vivo.

resultsFive LLPS-related biomarkers were screened by bioinformatics analyses to predict the osteosarcoma prognosis. These prognostic genes were significantly associated with the immune cell infiltration, tumor immune escape and drug sensitivity. Among them, WDR3 was a prognostic risk factor for osteosarcoma and stably bound to Nilotinib in the molecular docking model. In transfected U2-OS cells and xenograft mice, the downregulation of WDR3 significantly inhibited the malignant progression of osteosarcoma. More importantly, WDR3 could form droplets in U2-OS cells and restore the fluorescence intensity of WDR3 condensates with liquid-like behavior after photobleaching. The mutation in IDR impaired the phase separation ability of WDR3, whereas the fusion with hnRNAP1 IDR rescued the phase separation abnormality caused by WDR3 mutation. Moreover, the treatment with Nilotinib improved the progression of osteosarcoma in vivo and in vitro, while inhibiting the production of WDR3 phase-separated condensates.

conclusionWDR3 phase separation involves in the therapeutic mechanism of Nilotinib against osteosarcoma, and thus may serve as a potent biomarker to ameliorate adverse events following osteosarcoma treatment.

Indexed as

Bone NeoplasmsIntracellular Signaling Peptides and ProteinsOsteosarcomaPyrimidinesAnimalsBiomarkers, TumorCell Line, TumorCell ProliferationHumansMiceMolecular Docking SimulationPhase SeparationPrognosisXenograft Model Antitumor AssaysBiomarkers, TumorIntracellular Signaling Peptides and ProteinsnilotinibPyrimidinesIDR mutationLiquid-liquid phase separationNilotinibOsteosarcomaPrognostic biomarkerWDR3

Identifiers

PMID40646517
PMCPMC12247437

What Socratic 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 Socratic graph.