» Articles » PMID: 31632548

Overexpression of Rad51 Predicts Poor Prognosis and Silencing of Rad51 Increases Chemo-sensitivity to Doxorubicin in Neuroblastoma

Overview
Journal Am J Transl Res
Specialty General Medicine
Date 2019 Oct 22
PMID 31632548
Citations 12
Authors
Affiliations
Soon will be listed here.
Abstract

Outcome for children with high-risk neuroblastoma (NB) remains suboptimal. Recurrence and metastasis caused by chemo-resistance is an underlying mechanism contributing to the poor prognosis. Aberrant expression of Rad51 is implicated in both radio- and chemo-sensitivity in many human malignancies. However, its clinical significance and relationship with chemo-sensitivity in NB remain undefined. In this study, Rad51 expression was first evaluated in 70 surgically resected NB specimens by immunochemistry using tissue microarray and the correlation with clinic-pathologic features including survival was assessed. We then conducted microarray-based search with the Tumor Neuroblastoma public datasets to validate the immunochemistry results. Furthermore, the role of Rad51 in drug sensitivity was studied by using short hairpin RNA in the human NB SK-N-BE(2) and SH-SY5Y cells with treatment of doxorubicin. Our findings demonstrated for the first time that Rad51 is a prognostic marker in NB and down-regulation of Rad51 can lead to chemo-sensitizing effect in human NB cells.

Citing Articles

Copy-number dosage regulates telomere maintenance and disease-associated pathways in neuroblastoma.

Burkert M, Blanc E, Thiessen N, Weber C, Toedling J, Monti R iScience. 2024; 27(10):110918.

PMID: 39635126 PMC: 11615189. DOI: 10.1016/j.isci.2024.110918.


RAD51 is a poor prognostic marker and a potential therapeutic target for oral squamous cell carcinoma.

Tsai Y, Chan L, Chen Y, Su C, Hsu C, Wang Y Cancer Cell Int. 2023; 23(1):231.

PMID: 37798649 PMC: 10552296. DOI: 10.1186/s12935-023-03071-w.


A novel Cas9 fusion protein promotes targeted genome editing with reduced mutational burden in primary human cells.

Carusillo A, Haider S, Schafer R, Rhiel M, Turk D, Chmielewski K Nucleic Acids Res. 2023; 51(9):4660-4673.

PMID: 37070192 PMC: 10201422. DOI: 10.1093/nar/gkad255.


The Implication of Topoisomerase II Inhibitors in Synthetic Lethality for Cancer Therapy.

Matias-Barrios V, Dong X Pharmaceuticals (Basel). 2023; 16(1).

PMID: 36678591 PMC: 9866718. DOI: 10.3390/ph16010094.


Canine Mammary Tumor Cell Lines Derived from Metastatic Foci Show Increased RAD51 Expression but Diminished Radioresistance via p21 Inhibition.

Shimakawa K, Ochiai K, Hirose S, Tanabe E, Michishita M, Sakaue M Vet Sci. 2022; 9(12).

PMID: 36548864 PMC: 9784702. DOI: 10.3390/vetsci9120703.


References
1.
de Cremoux P, Jourdan-Da-Silva N, Couturier J, Tran-Perennou C, Schleiermacher G, Fehlbaum P . Role of chemotherapy resistance genes in outcome of neuroblastoma. Pediatr Blood Cancer. 2006; 48(3):311-7. DOI: 10.1002/pbc.20853. View

2.
Zhu J, Zhou L, Wu G, Konig H, Lin X, Li G . A novel small molecule RAD51 inactivator overcomes imatinib-resistance in chronic myeloid leukaemia. EMBO Mol Med. 2013; 5(3):353-65. PMC: 3598077. DOI: 10.1002/emmm.201201760. View

3.
Zhang Q, Zhang Q, Jiang X, Ye Y, Liao H, Zhu F . Collaborative ISL1/GATA3 interaction in controlling neuroblastoma oncogenic pathways overlapping with but distinct from MYCN. Theranostics. 2019; 9(4):986-1000. PMC: 6401405. DOI: 10.7150/thno.30199. View

4.
Wang Y, Chen K, Cai Y, Cai Y, Yuan X, Wang L . Annexin A2 could enhance multidrug resistance by regulating NF-κB signaling pathway in pediatric neuroblastoma. J Exp Clin Cancer Res. 2017; 36(1):111. PMC: 5559827. DOI: 10.1186/s13046-017-0581-6. View

5.
Szakacs G, Paterson J, Ludwig J, Booth-Genthe C, Gottesman M . Targeting multidrug resistance in cancer. Nat Rev Drug Discov. 2006; 5(3):219-34. DOI: 10.1038/nrd1984. View