Evidence map›Paper›PMID 35130920›Full record

ArticleMolecular cancer2022

Targeting HNRNPU to overcome cisplatin resistance in bladder cancer.

Zhen-Duo Shi, Lin Hao, Xiao-Xiao Han, Zhuo-Xun Wu, Kun Pang, Yang Dong, Jia-Xin Qin, Guang-Yue Wang, Xuan-Ming Zhang, Tian Xia and 9 more

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
25.1field-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

72 citing papers in PubMed, 122 citations in OpenAlex.

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12 more citing papers are in PubMed but not listed here.

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

19 authors at 7 institutions in 2 countries.

Zhen-Duo Shi *Department of Urology, Xuzhou Clinical School of Xuzhou Medical University, Jiangsu, China.
Lin Hao *Department of Urology, Xuzhou Clinical School of Xuzhou Medical University, Jiangsu, China.
Xiao-Xiao Han *Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Zhuo-Xun Wu *Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA.
Kun PangDepartment of Urology, Xuzhou Clinical School of Xuzhou Medical University, Jiangsu, China.
Yang DongDepartment of Urology, Xuzhou Clinical School of Xuzhou Medical University, Jiangsu, China.
Jia-Xin QinDepartment of Urology, Xuzhou Clinical School of Xuzhou Medical University, Jiangsu, China.
Guang-Yue WangGraduate School of Bengbu Medical College, Anhui, China.
Xuan-Ming ZhangDepartment of Urology, Xuzhou Clinical School of Xuzhou Medical University, Jiangsu, China.
Tian XiaDepartment of Urology, Xuzhou Clinical School of Xuzhou Medical University, Jiangsu, China.
Qing LiangDepartment of Urology, Xuzhou Clinical School of Xuzhou Medical University, Jiangsu, China.
Yan ZhaoDepartment of Urology, Xuzhou Clinical School of Xuzhou Medical University, Jiangsu, China.
Rui LiDepartment of Urology, Xuzhou Clinical School of Xuzhou Medical University, Jiangsu, China.
Shao-Qi ZhangNanjing Drum Tower Hospital Group, Suqian Hospital, Jiangsu, China.
Jun-Hao ZhangAffiliated Hospital of Guizhou Medical University, Guizhou, China.
Jian-Gang ChenDepartment of Urology, The Second Affiliated Hospital of Nantong University, Jiangsu, China.
Gong-Cheng WangDepartment of Urology, Huai'an First People's Hospital, Nanjing Medical University, Jiangsu, China.
Zhe-Sheng ChenDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA. chenz@stjohns.edu.ORCID 0000-0002-8289-097X
Cong-Hui HanDepartment of Urology, Xuzhou Clinical School of Xuzhou Medical University, Jiangsu, China. hanchdoctor@st.btbu.edu.cn.
Xuzhou Medical College · CNBengbu Medical College · CNSt. John's University · USGuiyang Medical University · CNNanjing Drum Tower Hospital · CNNantong University · CNShanghai First Maternity and Infant Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe overall response of cisplatin-based chemotherapy in bladder urothelial carcinoma (BUC) remains unsatisfactory due to the complex pathological subtypes, genomic difference, and drug resistance. The genes that associated with cisplatin resistance remain unclear. Herein, we aimed to identify the cisplatin resistance associated genes in BUC. EXPERIMENTAL 

designThe cytotoxicity of cisplatin was evaluated in six bladder cancer cell lines to compare their responses to cisplatin. The T24 cancer cells exhibited the lowest sensitivity to cisplatin and was therefore selected to explore the mechanisms of drug resistance. We performed genome-wide CRISPR screening in T24 cancer cells in vitro, and identified that the gene heterogeneous nuclear ribonucleoprotein U (HNRNPU) was the top candidate gene related to cisplatin resistance. Epigenetic and transcriptional profiles of HNRNPU-depleted cells after cisplatin treatment were analyzed to investigate the relationship between HNRNPU and cisplatin resistance. In vivo experiments were also performed to demonstrate the function of HNRNPU depletion in cisplatin sensitivity.

resultsSignificant correlation was found between HNRNPU expression level and sensitivity to cisplatin in bladder cancer cell lines. In the high HNRNPU expressing T24 cancer cells, knockout of HNRNPU inhibited cell proliferation, invasion, and migration. In addition, loss of HNRNPU promoted apoptosis and S-phase arrest in the T24 cells treated with cisplatin. Data from The Cancer Genome Atlas (TCGA) demonstrated that HNRNPU expression was significantly higher in tumor tissues than in normal tissues. High HNRNPU level was negatively correlated with patient survival. Transcriptomic profiling analysis showed that knockout of HNRNPU enhanced cisplatin sensitivity by regulating DNA damage repair genes. Furthermore, it was found that HNRNPU regulates chemosensitivity by affecting the expression of neurofibromin 1 (NF1).

conclusionsOur study demonstrated that HNRNPU expression is associated with cisplatin sensitivity in bladder urothelial carcinoma cells. Inhibition of HNRNPU could be a potential therapy for cisplatin-resistant bladder cancer.

Indexed as

Antineoplastic AgentsCarcinoma, Transitional CellUrinary Bladder NeoplasmsApoptosisCell Line, TumorCell ProliferationCisplatinDrug Resistance, NeoplasmHeterogeneous-Nuclear Ribonucleoprotein UHumansAntineoplastic AgentsCisplatinHeterogeneous-Nuclear Ribonucleoprotein UBladder urothelial carcinomaCisplatinGenome-wide CRISPR screeningHNRNPU

Identifiers

PMID35130920
PMCPMC8819945
OpenAlexW4210857378

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.