Overexpression of Rad51 predicts poor prognosis and silencing of Rad51 increases chemo-sensitivity to doxorubicin in neuroblastoma

Am J Transl Res. 2019 Sep 15;11(9):5788-5799. eCollection 2019.

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.

Keywords: Rad51; chemo-sensitivity; doxorubicin; drug resistance; neuroblastoma.