Evidence map›Paper›PMID 32661323›Full record

ArticleOncogene2020

Inhibiting Importin 4-mediated nuclear import of CEBPD enhances chemosensitivity by repression of PRKDC-driven DNA damage repair in cervical cancer.

Yang Zhou, Fei Liu, Qinyang Xu, Bikang Yang, Xiao Li, Shuheng Jiang, Lipeng Hu, Xueli Zhang, Lili Zhu, Qing Li and 8 more

Open access · hybridAbstract read
In one paragraph

Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

24 citing papers in PubMed, 42 citations in OpenAlex.

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  8. Hsa_circ_0101308 adjusted by N6-methyladenosine (mCancer biomarkers : section A of Disease markers · 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

18 authors at 5 institutions in 2 countries.

Yang Zhou *Department of Gynecology and Obstetrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, PR China.
Fei Liu *Department of Gynecology and Obstetrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, PR China.
Qinyang XuDepartment of Gynecology and Obstetrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, PR China.
Bikang YangDepartment of Gynecology and Obstetrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, PR China.
Xiao LiDepartment of Gynecology and Obstetrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, PR China.
Shuheng JiangState Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, PR China.
Lipeng HuState Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, PR China.
Xueli ZhangState Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, PR China.
Lili ZhuState Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, PR China.
Qing LiState Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, PR China.
Xiaolu ZhuDepartment of Gynecology and Obstetrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, PR China.
Hongfang ShaoCenter of Reproductive Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, PR China.
Miao DaiDepartment of Gynecologic Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, PR China.
Yifei ShenDepartment of Orthopedics, Shanghai East Hospital, School of Medicine, Shanghai Tongji University, Shanghai, 200120, PR China.
Bo NiDepartment of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200217, PR China.
Shuai WangJacobi medical center, bronx, New York, NY, 10461, USA.
Zhigang ZhangState Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, PR China. zzhang@shsci.org.ORCID http://orcid.org/0000-0001-8965-223X
Yincheng TengDepartment of Gynecology and Obstetrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, PR China. ycteng@sjtu.edu.cn.ORCID http://orcid.org/0000-0003-0772-3335
Shanghai Jiao Tong University · CNJiangsu University · CNCentral South University · CNJacobi Medical Center · USShanghai East Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cervical cancer (CC) remains highest in the mortality of female reproductive system cancers, while cisplatin (CDDP) resistance is the one of main reasons for the lethality. Preceding evidence has supported that karyopherins are associated with chemoresistance. In this study, we simultaneously compared CDDP-incomplete responders with CDDP-complete responders of CC patients and CDDP-insensitive CC cell lines with CDDP-sensitive group. We finally identified that DNA-PKcs (PRKDC) was related to CDDP sensitivity after overlapping in CC sample tissues and CC cell lines. Further functional assay revealed that targeting PRKDC by shRNA and NU7026 (specific PRKDC inhibitor) could enhance CDDP sensitivity in vitro and in vivo, which was mediated by impairing DNA damage repair pathway in CC. Mechanistically, we found that PRKDC was transcriptionally upregulated by CCAAT/enhancer-binding protein delta (CEBPD), while intriguingly, CDDP treatment strengthened the transcriptional activity of CEBPD to PRKDC. We further disclosed that Importin 4 (IPO4) augmented the nuclear translocation of CEBPD through nuclear localization signals (NLS) to activate PRKDC-mediated DNA damage repair in response to CDDP. Moreover, we demonstrated that IPO4 and CEBPD knockdown improved CDDP-induced cytotoxicity in vitro and in vivo. Together, we shed the novel insight into the role of IPO4 in chemosensitivity and provide a clinical translational potential to enhance CC chemosensitivity since the IPO4-CEBPD-PRKDC axis is actionable via NU7026 (PRKDC inhibitor) or targeting IPO4 in combination with CDDP.

Indexed as

Active Transport, Cell NucleusAnimalsAntineoplastic AgentsCCAAT-Enhancer-Binding Protein-deltaCell Line, TumorChromonesCisplatinDNA-Activated Protein KinaseDNA DamageDNA RepairDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticHeLa CellsHumansMembrane Transport Proteins2-(morpholin-4-yl)benzo(h)chromen-4-oneAntineoplastic AgentsCCAAT-Enhancer-Binding Protein-deltaCEBPD protein, humanChromonesCisplatinDNA-Activated Protein KinaseIPO4 protein, humanMembrane Transport ProteinsMorpholinesPRKDC protein, human

Identifiers

PMID32661323
PMCPMC7441007
OpenAlexW3041080899

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.