Evidence map›Paper›PMID 41455715›Full record

ArticleCell death & disease2025

ENO1-mediated deoxycytidine synthesis and gemcitabine resistance by stabilizing RRM2 in pancreatic cancer.

Yongning Li, Hao Wang, Liwen Chen, Yanyu Gong, Dijie Zheng, Futang Li, Changhao Wu, Zhiwei He, Chao Yu

Abstract read
In one paragraph

Article in Cell death & disease, 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

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
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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

9 authors.

Yongning Li *Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Hao Wang *Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Liwen Chen *Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Yanyu Gong *Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Dijie ZhengDepartment of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Futang LiDepartment of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
Changhao WuDepartment of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.ORCID http://orcid.org/0009-0001-4294-4275
Zhiwei HeDepartment of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.ORCID http://orcid.org/0000-0002-1434-2170
Chao YuDepartment of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China. yuchao2002@gmc.edu.cn.ORCID http://orcid.org/0000-0002-9244-9416

Funding

National Science Foundation of China | Key Programme 82303084, 82360519
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma is a highly malignant solid tumor of the digestive tract, and chemoresistance to gemcitabine is an important cause of shortened survival time in patients. Upregulation of deoxypyrimidine synthesis is one of the important reasons for pancreatic cancer cells to be resistant to gemcitabine, however, the specific mechanism leading to increased deoxypyrimidine synthesis in pancreatic cancer cells is still unclear. Ribonucleotide reductase M2 subunit (RRM2) is overexpressed through unclear mechanisms in many types of human cancer significantly affects sensitivity to various chemotherapy treatments. Here, we found that high expression of enolase-1 (ENO1) is closely related to gemcitabine resistance in pancreatic cancer patients. Cellular experiments and in vivo experiments confirmed that ENO1 increases the resistance of pancreatic cancer to gemcitabine without relying on its glycolytic enzyme activity. Mechanistically, ENO1 competitively binds to RRM2 with ubiquitin E3 ligase STUB1, thereby weakening the ubiquitination and degradation of RRM2 by STUB1. This ENO1-mediated aggregation of RRM2 protein increases the synthesis of dNTPs in pancreatic cancer cells, enhancing the resistance of pancreatic cancer to gemcitabine. Our study reveals a role of ENO1 in pancreatic cancer via RRM2-STUB1 axis and provides a scientific basis for the development of new therapeutic strategies targeting ENO1.

Indexed as

DeoxycytidineDNA-Binding ProteinsDrug Resistance, NeoplasmPancreatic NeoplasmsPhosphopyruvate HydrataseRibonucleoside Diphosphate ReductaseTumor Suppressor ProteinsAnimalsAntimetabolites, AntineoplasticCarcinoma, Pancreatic DuctalCell Line, TumorFemaleGemcitabineHumansMiceMice, Inbred BALB CAntimetabolites, AntineoplasticDeoxycytidineDNA-Binding ProteinsENO1 protein, humanGemcitabinePhosphopyruvate HydrataseRibonucleoside Diphosphate Reductaseribonucleotide reductase M2Tumor Suppressor ProteinsUbiquitin-Protein Ligases

Identifiers

PMID41455715
PMCPMC12847938

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