Evidence map›Paper›PMID 34006303›Full record

ArticleMolecular cancer2021

KDM6A-ARHGDIB axis blocks metastasis of bladder cancer by inhibiting Rac1.

Lei Liu, Jianfeng Cui, Yajing Zhao, Xiaochen Liu, Lipeng Chen, Yangyang Xia, Yong Wang, Shouzhen Chen, Shuna Sun, Benkang Shi and 1 more

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
11.5field-weighted citation impact, top 1% of its field
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

56 citing papers in PubMed, 84 citations in OpenAlex.

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  19. Histone demethylases in autophagy and inflammation.Cell communication and signaling : CCS · 2025
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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

11 authors at 4 institutions in 1 country.

Lei Liu *Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Jianfeng Cui *Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Yajing ZhaoDepartment of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Xiaochen LiuKey Laboratory for Experimental Teratology of Ministry of Education, Department of Medical Genetics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China.
Lipeng ChenDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Yangyang XiaDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Yong WangDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Shouzhen ChenDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Shuna SunDepartment of Dermatology, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong Provincial Hospital of Traditional Chinese Medicine, Jinan, China.
Benkang ShiDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. bkang68@sdu.edu.cn.
Yongxin ZouKey Laboratory for Experimental Teratology of Ministry of Education, Department of Medical Genetics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China. zouyongxin@sdu.edu.cn.
Shandong University · CNQilu Hospital of Shandong University · CNShandong University of Traditional Chinese Medicine · CNUniversity of Jinan · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundKDM6A, a histone demethylase, is frequently mutated in bladder cancer (BCa). However, the role and detailed molecular mechanism of KDM6A involved in bladder cancer progression remains unknown.

methodsTissue specimens were used to determine the expression levels and prognostic values of KDM6A and ARHGDIB. The MTT, colony formation, wound healing and Transwell migration and invasion assays were employed to detect the BCa cell proliferation, migration and invasion, respectively. Chemotaxis of macrophages was used to evaluate the ability of KDM6A to recruit macrophages. A subcutaneous tumour model and tail vein tumour injection in nude mice were used to assess the role of KDM6A in vivo. RNA sequencing, qPCR, Western blot, ChIP and phalloidin staining assay were performed to investigate the molecular functions of KDM6A. Dual-luciferase reporter assay was used to determine the effects of KDM6A and FOXA1 on the promoters of the ARHGDIB and KDM6A.

resultsWe showed that the KDM6A inhibited the motility and invasiveness of the BCa cells. Mechanistically, KDM6A promotes the transcription of ARHGDIB by demethylating histone H3 lysine di/trimethylation (H3K27me2/3) and consequently leads to inhibition of Rac1. EZH2, which catalyses the methylation of H3K27, functions to silence ARHGDIB expression, and an EZH2 inhibitor can neutralize the metastatic effect caused by KDM6A deficiency. Furthermore, we demonstrated that FOXA1 directly binds to the KDM6A promoter and thus transactivates KDM6A, leading to diminished metastatic potential.

conclusionOur findings establish the critical role of the FOXA1-KDM6A-ARHGDIB axis in restraining the malignancy of BCa and identify KDM6A and EZH2 as potential therapeutic targets in the management of BCa.

Indexed as

AnimalsCell MovementGene Expression Regulation, NeoplasticHeterograftsHistone DemethylasesHumansMiceMice, NudeNeoplasm Invasivenessrac1 GTP-Binding Proteinrho Guanine Nucleotide Dissociation Inhibitor betaUrinary Bladder NeoplasmsARHGDIB protein, humanHistone DemethylasesKDM6A protein, humanrac1 GTP-Binding ProteinRAC1 protein, humanrho Guanine Nucleotide Dissociation Inhibitor betaARHGDIB-Rac1 axisBladder cancerEpigeneticsFOXA1KDM6AMetastasis

Identifiers

PMID34006303
PMCPMC8130406
OpenAlexW3163738094

What OpenQuestion 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 OpenQuestion graph.