Oncotarget

Research Papers:

MiR-302a sensitizes leukemia cells to etoposide by targeting Rad52

Xiaoning Liu, Chun Heng, Yuanyuan Li and Liang Yu _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:73884-73891. https://doi.org/10.18632/oncotarget.17878

Metrics: PDF 1090 views  |   HTML 1741 views  |   ?  


Abstract

Xiaoning Liu1, Chun Heng1, Yuanyuan Li1 and Liang Yu2

1Central Laboratory, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu Province, 223300, China

2Hematology Department, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu Province, 223300, China

Correspondence to:

Liang Yu, email: yuliangha@163.com

Keywords: miR-302a, acute myeloid leukemia (AML), VP-16 resistance, Rad52

Received: August 08, 2016    Accepted: March 29, 2017    Published: May 16, 2017

ABSTRACT

miR-302a have been reported to participate in various physiological and pathological processes, however, a role for miR-302a in etoposide (VP-16) resistance of acute myeloid leukemia (AML) has not been reported. In this study, the aberrant expression of miR-302a was analyzed in patients with AML and in the AML HL-60 and U937 cell lines. Overexpression of miR-302a, by targeting the 3′UTR of Rad52, enhanced VP-16 sensitivity in the HL-60 and U937 cell. Accordingly, knockdown of Rad52 sensitized the HL-60 and U937 cells to VP-16-induced apoptosis and proliferation suppression. In addition, miR-302a enhanced the tumor-suppressive effect of VP-16 in a xenograft model of human HL-60 and U937 cell lines. Moreover, miR-302a repressed the AKT/Gsk3β/β-catenin pathway after Rad52 inhibition. Reintroduction of Rad52 reversed miR-302a-induced signaling suppression. The results of the present study demonstrated that miR-302a may be a target for the treatment of AML and a potential indicator of the therapeutic sensitivity of AML to VP-16.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 17878