Evidence map›Paper›PMID 40665360›Full record

ArticleJournal of translational medicine2025

Integration of scRNA-seq and ST-seq identifies hyperproliferative RRM2+ cells features and therapeutic targets in gastric cancer.

Shuai Ping, Xiong Jia, Yanan Tian

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Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

3 authors.

Shuai PingDepartment of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People's Republic of China.
Xiong JiaDepartment of Cardiology, Lihuili Hospital Affiliated to Ningbo University, Ningbo University, Ningbo, 315000, Zhejiang, China.
Yanan TianDepartment of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People's Republic of China. tianyn20@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDespite substantial progress in discovering novel therapeutic targets and compounds, cancer hyperproliferative cells (CHCs) play a central role in driving tumor progression in gastric cancer (GC). High-resolution single-cell RNA sequencing (scRNA-seq) integrated with spatial transcriptomics sequencing (ST-seq) elucidating the role of the CHC microenvironment in driving GC progression remains lacking.

methodsThrough integrated analysis of 40 scRNA-seq samples and 6 ST samples from human gastric tissues spanning tumor progression, we delineate the phenotypic plasticity of tumor epithelium and characterize the transcriptional trajectory from normal gastric cells to CHCs, a process associated with RRM2 overexpression. Finally, we validated the analysis results through cellular and animal experiments.

resultsOur findings demonstrate that RRM2 knockdown triggers ferroptosis in GC cells by promoting lipid peroxidation and intracellular iron accumulation. We further screen a compound and RRM2 inhibitor, osalmid, which effectively suppresses tumor growth in GC cell xenografts by triggering ferroptosis, thus offering a new therapeutic option for GC.

conclusionsThis study elucidates the critical role of RRM2 + CHCs in gastric cancer development and progression, providing novel insights for targeted therapies. The discovery of osalmid as a potential therapeutic agent offers a promising new treatment strategy for GC.

Indexed as

Molecular Targeted TherapyRibonucleoside Diphosphate ReductaseRNA-SeqSingle-Cell AnalysisStomach NeoplasmsAnimalsCell Line, TumorCell ProliferationFerroptosisGene Expression Regulation, NeoplasticHumansLipid PeroxidationMiceSingle-Cell Gene Expression AnalysisRibonucleoside Diphosphate Reductaseribonucleotide reductase M2FerroptosisGastric cancerSingle-cell sequencingSpatial transcriptomics

Identifiers

PMID40665360
PMCPMC12261629

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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.