Evidence map›Paper›PMID 28814318›Full record

ArticleJournal of experimental & clinical cancer research : CR2017

Annexin A2 could enhance multidrug resistance by regulating NF-κB signaling pathway in pediatric neuroblastoma.

Yi Wang, Kai Chen, Yihong Cai, Yuanxia Cai, Xiaojun Yuan, Lifeng Wang, Zhixiang Wu, Yeming Wu

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

27 citing papers in PubMed, 62 citations in OpenAlex.

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  13. Annexin Animal Models-From Fundamental Principles to Translational Research.International journal of molecular sciences · 2021
    Review
  14. Review
  15. Article
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  17. TRIM proteins in neuroblastoma.Bioscience reports · 2019
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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

8 authors at 2 institutions in 1 country.

Yi WangDepartment of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai, China.
Kai ChenDepartment of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai, China.
Yihong CaiDepartment of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai, China.
Yuanxia CaiDepartment of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai, China.
Xiaojun YuanPediatric Hematology & Oncology Department, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai, China.
Lifeng WangPathology Department, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai, China.
Zhixiang WuDepartment of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai, China. zhixiangwu@yahoo.com.
Yeming WuDepartment of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai, China. wuymsh@163.com.
Shanghai Jiao Tong University · CNXinHua Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChemotherapy is one of major therapeutic regimens for neuroblastoma (NB) in children. However, recurrence and metastasis associated with poor prognosis caused by acquired multidrug resistance remains a challenge. There is a great need to achieve new insight into the molecular mechanism of drug resistance in NB. The aim of this study is to identify novel drug sensitivity-related biomarkers as well as new therapeutic targets to overcome chemoresistance.

methodsWe proteome-wide quantitatively compared protein expression of two NB cell lines with different drug sensitivities, isolated from the same patient prior to and following chemotherapy. Annexin A2 (ANXA2) emerged as a key factor contributing to drug resistance in NB. Then, we assessed the correlation of ANXA2 expression and clinical characteristics using a tissue microarray. Further, the roles of ANXA2 in chemoresistance for NB and the underlying mechanisms were studied by using short hairpin RNA (shRNA) in vitro and vivo.

resultsFirst in total, over 6000 proteins were identified, and there were about 460 significantly regulated proteins which were up- or down-regulated by greater than two folds. We screened out ANXA2 which was upregulated by more than 12-fold in the chemoresistant NB cell line, and it might be involved in the drug resistance of NB. Then, using a tissue chip containing 42 clinical NB samples, we found that strong expression of ANXA2 was closely associated with advanced stage, greater number of chemotherapy cycles, tumor metastasis and poor prognosis. Following knockdown of ANXA2 in NB cell line SK-N-BE(2) using shRNA, we demonstrate enhanced drug sensitivity for doxorubicin (2.77-fold) and etoposide (7.87-fold) compared with control. Pro-apoptotic genes such as AIF and cleaved-PARP were upregulated. Inhibiting ANXA2 expression attenuated transcriptional activity of NF-κB via down-regulated nuclear translocation of subunit p50. Finally, simulated chemotherapy in a xenograft NB nude mouse model suggests that ANXA2 knockdown could improve clinical results in vivo.

conclusionOur profiling data provided a rich source for further study of the molecular mechanisms of acquired drug resistance in NB. Further study may determine the role of ANXA2 as a prognostic biomarker and a potential therapeutic target for patients with multidrug-resistant NB.

Indexed as

AnimalsAnnexin A2Cell Line, TumorCell ProliferationDoxorubicinDrug Resistance, MultipleDrug Resistance, NeoplasmGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiceNeoplasm ProteinsNeoplasm Recurrence, LocalNeuroblastomaNF-kappa BSignal TransductionAnnexin A2DoxorubicinNeoplasm ProteinsNF-kappa BANXA2ChemotherapyDrug resistanceNeuroblastomaNF-κBProteomics

Identifiers

PMID28814318
PMCPMC5559827
OpenAlexW2750470970

What OpenQuestion holds

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LicenceCC BY
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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.