Int J Biol Sci 2011; 7(2):221-233. doi:10.7150/ijbs.7.221
MiR-34a in Age and Tissue Related Radio-Sensitivity and Serum miR-34a as a Novel Indicator of Radiation Injury
1. Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Xiangyin Road, 200433, Shanghai, PR China;
2. Department of Obstetrics and Gynecology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
# These authors contributed equally to this work.
Liu C, Zhou C, Gao F, Cai S, Zhang C, Zhao L, Zhao F, Cao F, Lin J, Yang Y, Ni J, Jia J, Wu W, Zhou L, Cui J, Zhang W, Li B, Cai J. MiR-34a in Age and Tissue Related Radio-Sensitivity and Serum miR-34a as a Novel Indicator of Radiation Injury. Int J Biol Sci 2011; 7(2):221-233. doi:10.7150/ijbs.7.221. Available from http://www.ijbs.com/v07p0221.htm
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.
Keywords: Radio-sensitivity, MicroRNA, MiR-34a, P53, Bcl-2, Apoptosis.