Evidence map›Paper›PMID 41307804›Full record

ArticleMolecular biomedicine2025

Ubiquitin-specific protease 13 promotes colorectal cancer progression by stabilizing mitogen-activated protein kinase kinase 3.

Si-Yu Chang, Bo Gu, Yong Xiong, Meng-Si Zhao, Le Li, Yi Liu, Bai-Qi Wang, Guo-Qing Li, Run-Lei Du, Xiao-Dong Zhang

Abstract read
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In one paragraph

Article in Molecular biomedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Si-Yu Chang *National Health Commission Key Laboratory of Birth Defect Research and Prevention, MOE Key Lab of Rare Pediatric Diseases, Hunan Provincial Key Laboratory of Basic and Clinical Pharmacological Research of Gastrointestinal Cancer, The Second Affiliated Hospital, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, China.
Bo Gu *Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, China.
Yong XiongNational Health Commission Key Laboratory of Birth Defect Research and Prevention, MOE Key Lab of Rare Pediatric Diseases, Hunan Provincial Key Laboratory of Basic and Clinical Pharmacological Research of Gastrointestinal Cancer, The Second Affiliated Hospital, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, China.
Meng-Si ZhaoNational Health Commission Key Laboratory of Birth Defect Research and Prevention, MOE Key Lab of Rare Pediatric Diseases, Hunan Provincial Key Laboratory of Basic and Clinical Pharmacological Research of Gastrointestinal Cancer, The Second Affiliated Hospital, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, China.
Le LiNational Health Commission Key Laboratory of Birth Defect Research and Prevention, MOE Key Lab of Rare Pediatric Diseases, Hunan Provincial Key Laboratory of Basic and Clinical Pharmacological Research of Gastrointestinal Cancer, The Second Affiliated Hospital, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, China.
Yi LiuNational Health Commission Key Laboratory of Birth Defect Research and Prevention, MOE Key Lab of Rare Pediatric Diseases, Hunan Provincial Key Laboratory of Basic and Clinical Pharmacological Research of Gastrointestinal Cancer, The Second Affiliated Hospital, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, China.
Bai-Qi WangNational Health Commission Key Laboratory of Birth Defect Research and Prevention, MOE Key Lab of Rare Pediatric Diseases, Hunan Provincial Key Laboratory of Basic and Clinical Pharmacological Research of Gastrointestinal Cancer, The Second Affiliated Hospital, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, China.
Guo-Qing LiNational Health Commission Key Laboratory of Birth Defect Research and Prevention, MOE Key Lab of Rare Pediatric Diseases, Hunan Provincial Key Laboratory of Basic and Clinical Pharmacological Research of Gastrointestinal Cancer, The Second Affiliated Hospital, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, China.
Run-Lei DuNational Health Commission Key Laboratory of Birth Defect Research and Prevention, MOE Key Lab of Rare Pediatric Diseases, Hunan Provincial Key Laboratory of Basic and Clinical Pharmacological Research of Gastrointestinal Cancer, The Second Affiliated Hospital, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, China. runleidu@whu.edu.cn.
Xiao-Dong ZhangNational Health Commission Key Laboratory of Birth Defect Research and Prevention, MOE Key Lab of Rare Pediatric Diseases, Hunan Provincial Key Laboratory of Basic and Clinical Pharmacological Research of Gastrointestinal Cancer, The Second Affiliated Hospital, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, China. zhangxd@usc.edu.cn.ORCID 0000-0002-5137-7145

Funding

Foundation of Hunan Provincial Key Laboratory 2023TP1014Fund Project of University of South China 221RGC003Hunan Provincial Department of Education Scientific Research Project 24B0408National Natural Science Foundation of China 32370777National Natural Science Foundation of China 32570837Natural Science Foundation of Hunan Province 2023JJ60049Natural Science Foundation of Hunan Province 2024JJ6379
6 · The paper itself

Abstract

The deubiquitinase ubiquitin-specific protease 13 (USP13) has been implicated in various cancers, yet its precise molecular function and clinical significance in colorectal cancer (CRC) remain poorly defined. Here, we identify USP13 as a critical regulator of CRC progression through systematic investigation of its impact on oncogenic signaling pathways. Using luciferase-based pathway screening, we discovered that USP13 activates the mitogen-activated protein kinase (MAPK) signaling cascade. USP13 directly interacts with and stabilizes mitogen-activated protein kinase kinase 3 (MKK3), a key upstream kinase of the p38/MAPK pathway, through removal of K48-linked ubiquitination at the K32 residue. This deubiquitination process requires the UBA domain of USP13 and prevents proteasomal degradation of MKK3, leading to enhanced p38 phosphorylation and activation. Functional validation demonstrated that USP13 and MKK3 significantly promotes CRC cell proliferation, migration, and invasion in vitro. Importantly, in vivo xenograft experiments confirmed that USP13-driven tumor growth depends on MKK3 and can be rescued by constitutive p38 activation. Clinical correlation analysis of CRC patient specimens revealed a strong positive correlation between USP13 and MKK3 expression levels, with elevated USP13 expression associated with advanced disease stage. Our findings not only establish the USP13-MKK3-p38 axis as a crucial molecular pathway in CRC progression but also identify USP13 as a promising therapeutic target.

Indexed as

Colorectal NeoplasmsMAP Kinase Kinase 3Ubiquitin-Specific ProteasesAnimalsCell Line, TumorCell MovementCell ProliferationDisease ProgressionEnzyme StabilityFemaleHumansMAP Kinase Signaling SystemMiceMice, Nudep38 Mitogen-Activated Protein KinasesPhosphorylationMAP2K3 protein, humanMAP Kinase Kinase 3p38 Mitogen-Activated Protein KinasesUbiquitin-Specific ProteasesUSP13 protein, humanColorectal cancerDeubiquitinationMKK3P38 MAPK signalingTumor progressionUSP13

Identifiers

PMID41307804
PMCPMC12660564

What Socratic holds

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Registered trials

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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 Socratic graph.