Evidence map›Paper›PMID 40683967›Full record

ArticleScientific reports2025

Genome-wide CRISPR/Cas9 screening identifies PTGR2 as a potential therapeutic target for sunitinib resistance in clear cell renal cell carcinoma.

Wei Chang, Biao Zhang, Shujun Yang, Xingxing Zhang, Lili Zhang, Su Zhang, Jianzhong Lu, Wei Wang, Panfeng Shang, Zhongjin Yue

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 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
–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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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.

Wei Chang *Institute of Urology, Lanzhou University Second Hospital, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Lanzhou, 730030, Gansu, China.
Biao Zhang *Institute of Urology, Lanzhou University Second Hospital, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Lanzhou, 730030, Gansu, China.
Shujun Yang *Institute of Urology, Lanzhou University Second Hospital, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Lanzhou, 730030, Gansu, China.
Xingxing ZhangInstitute of Urology, Lanzhou University Second Hospital, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Lanzhou, 730030, Gansu, China.
Lili ZhangInstitute of Urology, Lanzhou University Second Hospital, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Lanzhou, 730030, Gansu, China.
Su ZhangInstitute of Urology, Lanzhou University Second Hospital, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Lanzhou, 730030, Gansu, China.
Jianzhong LuInstitute of Urology, Lanzhou University Second Hospital, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Lanzhou, 730030, Gansu, China.
Wei WangInstitute of Urology, Lanzhou University Second Hospital, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Lanzhou, 730030, Gansu, China. wangwei2011@lzu.edu.cn.
Panfeng ShangInstitute of Urology, Lanzhou University Second Hospital, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Lanzhou, 730030, Gansu, China. shangpf@lzu.edu.cn.
Zhongjin YueInstitute of Urology, Lanzhou University Second Hospital, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Lanzhou, 730030, Gansu, China. yuezj@lzu.edu.cn.

Funding

Cuiying Science and Technology Innovation Plan Project of Lanzhou University Second Hospital CY2021-MS-A11Gansu Provincial Natural Science Foundation 22JR5RA1009Gansu Provincial Science Fund for Distinguished Young Scholars 22JR5RA942Medical Innovation and Development Project of Lanzhou University lzuyxcx-2022-105the Special Fund Project for Doctoral Training Program of Lanzhou University Second Hospital PR5124025
6 · The paper itself

Abstract

Acquired and intrinsic resistance to sunitinib is a major obstacle to improving the therapeutic efficacy of treatment for clear cell renal cell carcinoma (ccRCC). This study aimed to identify novel therapeutic targets and the potential molecular mechanisms to overcome sunitinib resistance in ccRCC. Utilizing genome-wide CRISPR/Cas9 screening and resistant transcriptomics, we identified that prostaglandin reductase 2 (PTGR2) is a novel therapeutic target to overcome sunitinib resistance in ccRCC. The silencing of PTGR2 enhanced the cytotoxic effects of sunitinib in ccRCC cells, as measured by cell viability assays, and suppressed tumor growth in xenograft models. Mechanistically, PTGR2 physically interacts with lysine specific demethylase 6A (KDM6A) via endogenous/exogenous co-immunoprecipitation. PTGR2 knockdown reduced KDM6A protein expression, while KDM6A overexpression partially reversed the sensitization effect of PTGR2 silencing, suggesting KDM6A is a major downstream effector. Our findings establish the PTGR2-KDM6A axis as a potential target for overcoming sunitinib resistance in ccRCC. Pharmacological inhibition of PTGR2 or targeted modulation of KDM6A activity represents a promising combination strategy to overcome sunitinib resistance and improve patient outcomes.

Indexed as

Carcinoma, Renal CellCRISPR-Cas SystemsDrug Resistance, NeoplasmKidney NeoplasmsSunitinibAnimalsAntineoplastic AgentsCell Line, TumorGene Expression Regulation, NeoplasticHistone DemethylasesHumansMiceXenograft Model Antitumor AssaysAntineoplastic AgentsHistone DemethylasesKDM6A protein, humanSunitinibDrug resistanceGenome-wide CRISPR/Cas9 screeningKDM6APTGR2Renal cell carcinomaSunitinib

Identifiers

PMID40683967
PMCPMC12276353

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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.