miR-27b-3p a Negative Regulator of DSB-DNA Repair

Abstract

Understanding the regulation of DNA repair mechanisms is of utmost importance to identify altered cellular processes that lead to diseases such as cancer through genomic instability. In this sense, miRNAs have shown a crucial role. Specifically, miR-27b-3 biogenesis has been shown to be induced in response to DNA damage, suggesting that this microRNA has a role in DNA repair. In this work, we show that the overexpression of miR-27b-3p reduces the ability of cells to repair DNA lesions, mainly double-stranded breaks (DSB), and causes the deregulation of genes involved in homologous recombination repair (HRR), base excision repair (BER), and the cell cycle. DNA damage was induced in BALB/c-3T3 cells, which overexpress miR-27b-3p, using xenobiotic agents with specific mechanisms of action that challenge different repair mechanisms to determine their reparative capacity. In addition, we evaluated the expression of 84 DNA damage signaling and repair genes and performed pathway enrichment analysis to identify altered cellular processes. Taken together, our results indicate that miR-27b-3p acts as a negative regulator of DNA repair when overexpressed.