17q12-2。研究表明，BRCA1基因参与调控细胞周期，诱导DNA损伤修复、细胞凋亡、控制基因转录、泛素化等重要的细胞活动，是维持细胞基因组稳定的重要调控因子。
Shen等[20]在乳腺癌研究中提出，miRNA可以调控多种抑癌基因和原癌基因。miRNA的遗传变异可调控这些基因的表达，从而导致肿瘤的易感性。更多研究[21]表明，miR-146a可特异的结合BRCA1/BRCA2是3'UTR，因此BRCA1/BRCA2是miR-146a的潜在靶点。体外将miR-146a转入乳腺癌MCF-7细胞后检测发现，BRCA1/BRCA2表达抑制情况具有统计学差异，证实了miR-146a通过抑制BRCA1/BRCA2表达从而使乳腺癌、卵巢癌的易感性明显增强。
4.4调控p53基因的miRNA
P53基因是目前发现的最为重要的抑癌基因，与细胞生长、凋亡、癌变等关系密切，在大肠癌、肝癌、胃癌等恶性肿瘤中的突变率在50％以上。近年来对p53下游靶基因的研究突飞猛进，特别是与miRNA研究相结合，发现其通过调节miR-34家族及miR-29家族表达发挥细胞关卡作用，参与细胞基因损伤修复、细胞程序性死亡等重要环节。但对以p53基因为靶点的miRNA的研究却不多见。
Le等[22]对神经系统内敢表达的miR-125b研究发现，miR-125b在斑马鱼和人类中可下调p53基因的表达及p53蛋白的合成，并进一步发现在放疗或羟基喜树碱化疗后，miR-125b表达明显降低，相应的p53蛋白的表达在DNA损伤细胞中明显增加，充分说明了p53
为miR-125b的靶点之一。此后，Zhang’等[23]发现miR-125b的靶点也是p53基因，这不难推想miR-125家族通过抑制p53基因表达使细胞对DNA损伤修复能力减弱，以及抑制凋亡从而导致癌症的发生。除miR-125家族外，Xie、Tian等[24-25]报道miR-106、miR-150、miR-1285下调的同时，p53的表达明显升高，经检测其都可以和p53转录产物的3'UTR结合，充分说明p53为多个miRNA的靶点，受到miRNA网络的调控。 5、结语
细胞DNA受到损伤后，将会激发一系列生物学行为，导致多个DNA损伤修复基因及多条修复路径的激活。而这一切生物学行为都将受到miRNA网络的调控。到底有多少miRNA可以调控DNA损伤修复还不清楚，其具体调节机制也有待于进一步探求。随着对DNA损伤基因、途径及miRNA调控网络了解的不断深入，将可能为DNA损伤相关肿瘤的发生、发展提供新的线索，同时也为肿瘤的诊断和治疗提供新的思路和策略。
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