Differential regulation of MicroRNA expression in irradiated and bystander cells

Abstract

The ionizing radiation (IR) induces a variety of biological effects in irradiated cells. Additionally, the irradiated cells communicate with unirradiated cells and induce changes in them through a phenomenon termed as the bystander effect. The nature of the bystander effect signal and how it impacts unirradiated cells remains to be discovered. Examination of molecular changes in bystander cells due to signals from irradiated cells could lead to the identification of the pathways underlying the bystander effect. To gain insight into the molecular pathways affected by the transmission of signal from irradiated cells to bystander cells, we monitored the microRNA (miRNA) transcriptional changes. miRNAs control gene expression at the posttranscriptional level. In previous studies from our laboratory the modulation of miRNA in irradiated human cells were identified. In the present work human lymphoblasts TK6 cells in a medium exchanged bystander effect model system were used to analyze miRNA expression alterations by employing the real time RT-PCR technology. The relative expression of several miRNAs involved in RAS, c-MYC and BCL2 gene regulation were examined. The let-7 family of miRNAs was upregulated in irradiated cells but most of these miRNAs remained repressed in bystander cells. The miR-17-3p, miR-19b, and miR-18a were upregulated in irradiated cells but were repressed in the bystander cells. The miR-17-5p, miR-142-3p, miR-142-5p, and miR-19a were induced only for a short time in bystander cells. The miR-15a, miR-16, miR-143, miR-145, miR-155, and miR21 were upregulated in irradiated TK6 cells. While the expression of miR-15a, miR-16, miR-155, and miR-21 was repressed, the miR-143 and miR-145 expression was induced in bystander cells. These results indicate the involvement of miRNA modulation in irradiated and bystander cells.