RAD52 aptamer regulates DNA damage repair and STAT3 in BRCA1/BRCA2‑deficient human acute myeloid leukemia.

Abstract

RAD52 (Radiation sensitive 52) is a key factor in DNA damage repair (DDR) bypass, which participates in single-strand annealing (SSA) after DNA damage end excision, while breast cancer type 1 susceptibility protein (BRCA1)/breast cancer type 2 susceptibility protein (BRCA2) play critical roles in homologous recombination (HR) repair. The present study aimed to determine whether RAD52-induced regulation of repair bypass occurs in acute myeloid leukemia (AML) cells and to explore the underlying mechanism. Herein, we applied an RAD52 aptamer to AML cells with downregulated BRCA1/2. RAD52 aptamer inhibited AML cell proliferation detected by cell counting, promoted cell apoptosis obtained by flow cytometry, and suppressed DNA damage repair behavior measured by comet assay and flow cytometry, after drug intervention during low expression of BRCA1/2. During this process, DDR-related cell cycle checkpoint proteins were activated, and the cells were continuously arrested in the S/G2 phase, which affected the cell damage repair process. Concurrently, the expression levels of apoptosis-related proteins were also altered. Furthermore, the expression of STAT3 and p-STAT3 was downregulated by the RAD52 aptamer, suggesting that RAD52 affects the STAT3 signaling pathway. In summary, we present a possible role for RAD52 in DDR of BRCA1/2-deficient AML cells that involves the STAT3 signaling pathway.