MiR-34a in Age and Tissue Related Radio-Sensitivity and Serum miR-34a as a Novel Indicator of Radiation Injury

Abstract

MiR-34a, a direct target of p53, has shown to exert potent anti-proliferative effects. It has also been found that miR-34a can be induced by irradiation in vitro and in vivo. However, the relationship between miR-34a and radio-sensitivity, and its potential diagnostic significance in radiation biology, remain unclear. This study found that differing responses to ionizing radiation (IR) of young and adult mice were related to miR-34a. First, we found that miR-34a could be induced in many organs by radiation of both young and adult mice. However, the level of miR-34a induced by young mice was much higher when compared to adult mice. Next, we found that miR-34a played a critical role in radio-sensitivity variations of different tissues by enhancing cell apoptosis and decreasing cell viability. We also found that the induction of miR-34a by radiation was in a p53 dependent manner and that one possible downstream target of miR-34a that lead to different radio-sensitivity was the anti-apoptosis molecular Bcl-2. However, over-expression of miR-34a and knockdown of Bcl-2 could significantly enhance the radio-sensitivity of different cells while inhibition of miR-34a could protect cells from radiation injury. Finally, we concluded that miR-34a could be stable in serum after IR and serve as a novel indicator of radiation injury. Taken together, this data strongly suggests that miR-34a may be a novel indicator, mediator and target of radiation injury, radio-sensitivity and radioprotection.