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

Oncotarget
Xiaoning LiuLiang Yu

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.

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Citations

Sep 7, 2018·Leukemia & Lymphoma·Chengcheng HeXiaoli Zheng
Feb 15, 2018·Frontiers in Oncology·Stephanie Rebecca SetijonoSu Jung Song
Oct 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Seung Wan SonJong Kook Park
May 14, 2019·Journal of Cellular Biochemistry·Hossein SharifiMohsen Taghizadeh

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Methods Mentioned

BETA
transfection
flow cytometry
xenograft
density-gradient centrifugation
Assay
protein assay

Software Mentioned

miRDB
TargetScan
miRanda

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