microRNAs in cancer cell response to ionizing radiation.

SIGNIFICANCE: microRNAs (miRNA) have been characterized as master regulators of the genome. As such, miRNAs are responsible for regulating almost every cellular pathway, including the DNA damage response (DDR) after ionizing radiation (IR). IR is a therapeutic tool that is used for the treatment of several types of cancer, yet the mechanism behind radiation response is not fully understood. RECENT ADVANCES: It has been demonstrated that IR can alter miRNA expression profiles, varying greatly from one cell type to the next. It is possible that this variation contributes to the range of tumor cell responsiveness that is observed after radiotherapy, especially considering the extensive role for miRNAs in regulating the DDR. In addition, individual miRNAs or miRNA families have been shown to play a multifaceted role in the DDR, regulating multiple members in a single pathway. CRITICAL ISSUES: In this review, we will discuss the effects of radiation on miRNA expression as well as explore the function of miRNAs in regulating the cellular response to radiation-induced damage. We will discuss the importance of miRNA regulation at each stage of the DDR, including signal transduction, DNA damage sensing, cell cycle checkpoint activation, DNA double-strand break repair, and apoptosis. We will focus on emphasizing the importance of a single miRNA targeting several mediators within a pathway. FUTURE DIRECTIONS: miRNAs will continue to emerge as critical regulators of the DDR. Understanding the role of miRNAs in the response to IR will provide insights for improving the current standard therapy.