Distinct Sets of lncRNAs are Differentially Modulated after Exposure to High and Low Doses of X Rays.

Abstract

High- and low-dose X rays are used in medicine as therapeutic and diagnostic tools, respectively. While the cellular response to high-dose radiation is well known, studies on the effects of low-dose radiation and its ability to trigger a proper DNA damage response have had contradictory results. The functions of many signaling and effector proteins of the DNA damage response (DDR) have been described, and are attributed to well-known DDR pathways. However, there has been little known about the contribution of long noncoding RNAs (lncRNAs) to DDR, although there is recent evidence that lncRNAs may be associated with almost all biological functions, including DDR. In this work, we investigated the participation of lncRNAs in the response to different X-ray doses. By microarray analysis, we observed that in human breast epithelial cells, distinct sets of coding and noncoding transcripts are differentially regulated after moderate- and high-dose irradiation compared to those regulated after low-dose irradiation. While the modulated coding and noncoding genes at low doses relate to cell signaling pathways, those affected by moderate and high doses are mostly enriched for cell cycle regulation and apoptotic pathways. Quantification using qPCR of the lncRNAs identified by microarrays allowed the validation of 75% of those regulated at the higher doses. These results indicate that lncRNA expression is regulated by ionizing radiation and that this expression is dose dependent.