Evidence map›Paper›PMID 39814224›Full record

ArticleJournal of advanced research2025

Activation of sphingosine-1-phosphate receptor 2 (S1PR2) upregulates dihydropyrimidine dehydrogenase (DPD) expression in colon cancer cells.

Zhi-Kun Guo, Xin-Feng Wu, Ming-Yong Tan, Wei-Shi Liang, Yu-Meng Yang, Zhen-Zhen Chu, Rui Xu, Ke-Qin Li, Yu-Yao Cheng, Ying-Zhi Zhang and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 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. 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

14 authors.

Zhi-Kun GuoToxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, China; Department of Gastroenterology, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, China.
Xin-Feng WuPharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Ming-Yong TanToxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, China.
Wei-Shi LiangJoint Laboratory for Research & Treatment of Spinal Cord Injury in Spinal Deformity, Capital Medical University, Beijing, China; Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Yu-Meng YangBeijing Key Laboratory for Tumor Invasion and Metastasis, Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, China.
Zhen-Zhen ChuKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Lymphoma Department, Peking University Cancer Hospital & Institute, Beijing, China.
Rui XuPharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Ke-Qin LiPharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Yu-Yao ChengToxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, China.
Ying-Zhi ZhangToxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, China.
Yu-Hang ZhangPharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Yong HaiJoint Laboratory for Research & Treatment of Spinal Cord Injury in Spinal Deformity, Capital Medical University, Beijing, China; Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China. Electronic address: yong.hai@ccmu.edu.cn.
Shu-Xiang CuiToxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, China; Joint Laboratory for Research & Treatment of Spinal Cord Injury in Spinal Deformity, Capital Medical University, Beijing, China. Electronic address: cuisx@ccmu.edu.cn.
Xian-Jun QuPharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China; Joint Laboratory for Research & Treatment of Spinal Cord Injury in Spinal Deformity, Capital Medical University, Beijing, China. Electronic address: qxj@ccmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionDihydropyrimidine dehydrogenase (DPD) is a major determinant of cancer 5-fluorouracyl (5-FU) resistance via its direct degradation. However, the mechanisms of tumoral DPD upregulation have not been fully understood.

objectivesThis study aimed to explore the role of S1PR2 in the regulation of tumoral DPD expression, identifying S1PR2 as the potential target for reversing 5-FU resistance.

methodsWestern blot was used to analyze S1PR2 expression in cultured cancer cells and human colorectal cancer (CRC) tissues. 5-FU resistance was estimated in mouse xenografts of HT-29

resultsS1PR2 was highly expressed in cancer cell lines and human CRC tissues. Activation of S1PR2 upregulated DPD expression, leading to 5-FU resistance. Mechanistically, activated S1PR2 upregulated nuclear TWIST1 by activating the Hippo/TEAD1-TWIST1 pathway. Nuclear TWIST1 interacted with the JMJD3-RNA Pol II complex, resulting in the interaction of TWIST1 with the DPYD promoter, thus increasing H3K27me3-enriched DPYD transcription. These findings were confirmed in xenografted human colon cancer cells in nude mice. Transfection with an S1PR2 expression vector led to the upregulation of DPD, blunting the sensitivity of SW480

conclusionsActivation of S1PR2 upregulated DPD expression by activating the Hippo/TWIST1-JMJD3 pathway. S1PR2 is therefore a potential target for novel inhibitors that may reverse 5-FU resistance in cancer therapy.

Indexed as

Colonic NeoplasmsDihydrouracil Dehydrogenase (NADP)Sphingosine-1-Phosphate ReceptorsAnimalsCell Line, TumorDrug Resistance, NeoplasmFluorouracilGene Expression Regulation, NeoplasticHT29 CellsHumansMiceMice, NudeUp-RegulationXenograft Model Antitumor AssaysDihydrouracil Dehydrogenase (NADP)FluorouracilS1PR2 protein, humanSphingosine-1-Phosphate Receptors5-FU resistanceDihydropyrimidine dehydrogenase (DPD)DPYD promoterHippo/TWIST1-JMJD3 pathwayS1PR2

Identifiers

PMID39814224
PMCPMC12627388

What Socratic 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 Socratic graph.