MiR-34a in age and tissue related radio-sensitivity and serum miR-34a as a novel indicator of radiation injury.
MiR-34a in age and tissue related radio-sensitivity and serum miR-34a as a novel indicator of radiation injury.
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年龄和组织相关放射敏感性中的 MiR-34a 以及血清 miR-34a 作为放射损伤的新指标
DOI：
10.7150/ijbs.7.221
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发表时间：
2011-03-02
影响因子：
9.2
通讯作者：
Cai J
中科院分区：
文献类型：
--
作者：
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是p53的直接靶点，已被证明具有强大的抗增殖作用。研究还发现，miR-34a在体内和体外均可被辐照诱导。然而，miR-34a与放射敏感性之间的关系及其在放射生物学中的潜在诊断意义尚不清楚。本研究发现，年轻和成年小鼠对电离辐射（IR）的不同反应与miR-34a有关。首先，我们发现miR-34a可以在幼年和成年小鼠的许多器官中被辐射诱导。然而，与成年小鼠相比，年轻小鼠诱导的miR-34a水平要高得多。接下来，我们发现miR-34a通过增强细胞凋亡和降低细胞活力，在不同组织的放射敏感性变化中发挥关键作用。我们还发现，辐射对miR-34a的诱导是p53依赖的，miR-34a导致不同放射敏感性的一个可能的下游靶点是抗凋亡分子Bcl-2。然而，过表达miR-34a和敲低Bcl-2可显著增强不同细胞的辐射敏感性，抑制miR-34a可保护细胞免受辐射损伤。最后，我们得出结论，miR-34a在IR后的血清中是稳定的，可以作为一种新的辐射损伤指标。综上所述，这些数据强烈表明miR-34a可能是辐射损伤、辐射敏感性和辐射防护的一种新的指标、介质和靶标。
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.
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影响因子：
9.2
作者：
Deng Y;Deng H;Bi F;Liu J;Bemis LT;Norris D;Wang XJ;Zhang Q
通讯作者：
Zhang Q
影响因子：
4.8
作者：
Ahmed, MM;Alcock, A;Freeman, JW
通讯作者：
Freeman, JW
影响因子：
2.6
作者：
DOLL, R
通讯作者：
DOLL, R
影响因子：
64.8
作者：
CROSFILL, ML;LINDOP, PJ;ROTBLAT, J
通讯作者：
ROTBLAT, J
影响因子：
64.8
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.