microRNAs in Cancer Cell Response to Ionizing Radiation

Abstract

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. Antioxid. Redox Signal. 21, 293-312.

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy

“…Several signaling pathways, including PI3K/AKT, mitogen-activated protein kinase and ATM/CHK2/p53, have been linked to the tumor radioresistance. 22,23 In the present study we have demonstrated that IKKα-mediated miR-196a biogenesis regulates the sensitivity of NPC cells to radiotherapy. Dephosphorylation of p-IKKαT23 downregulates miR-196a expression and promotes the resistance of NPC cells to radiation treatment.…”

Expression Signature and Role of miR-30d-5p in Non-Small Cell Lung Cancer: a Comprehensive Study Based on in Silico Analysis of Public Databases and in Vitro Experiments

“…More than 1000 miRNAs have been identified in humans and are predicted to modulate the expression of at least 60% of protein-coding genes at the transcriptional level [11][12][13]. By repressing target genes, miRNAs play key roles in various biological events in tumors, such as cell proliferation, differentiation, apoptosis and tumor invasion [14][15][16][17][18].…”

Emerging role of microRNAs in breast cancer radiotherapy

“…MiRNAs are involved in regulating at the post-transcriptional level the expression of important targets in the DDR pathway [14,15] . Indeed, miRNAs have been shown to efficiently modulate tumor radiosensitivity by blocking both the NHEJ and HR repair pathways involved in the DDR; they have proven to interfere with the major pathways activated by ionizing radiation, such as the PI3-K/Akt, NF-κB, MAPK and TGFβ signaling pathways [16] .…”