非编码RNA对血友病A的调控机制研究进展

Research progress on the mechanism of non-coding RNA regulation of hemophilia A

血友病是一种遗传性凝血功能异常的出血性疾病,包括血友病A和血友病B等不同类型,主要临床表现为关节、肌肉和深部组织自发或者创伤后反复出血,常幼年起病并累及终身。血友病的治疗以替代治疗为主,补充相应的凝血因子,此外还有双特异性单克隆抗体等非因子药物治疗以及基因治疗等。近年来,血友病A发病机制的研究取得较大进展,不再局限于凝血因子基因编码序列的突变是引起血友病的唯一原因。许多研究发现,非编码RNA(ncRNA)的异常表达参与调控凝血因子Ⅷ(FⅧ) mRNA和蛋白的表达,不仅解释了FⅧ基因型正常的患者仍然表现为血友病A,也为理解其他血友病类型的发病机制提供了新的方向。本文就ncRNA调控血友病A的机制研究进展进行综述。

Hemophilia,which includes different types such as hemophilia A and hemophilia B,is a hemorrhagic disorder with inherited blood clotting abnormalities.The main clinical manifestations are spontaneous bleeding of joints,muscles and deep tissues or repeated bleeding after trauma.It often starts at an early age and affects the whole life.The treatment of hemophilia patients is still dominated by alternative therapy,supplementing the corresponding clotting factors.In addition,non-factor drug therapy is adopted such as bispecific monoclonal antibodies and gene therapy.In recent years,the research on the pathogenesis of hemophilia A has made great progress,which is no longer limited to the mutation of the coding sequence of coagulation factor gene as the only cause of hemophilia.Many studies have found that abnormal expression of non-coding RNA(ncRNA)is involved in the regulation of coagulation factorⅧ(FⅧ)mRNA and protein,which not only explains why patients with normal FⅧgenotypes still present with hemophilia A,but also provides new directions for understanding the pathogenesis of other types of hemophilia.This paper reviews the research progress on the regulatory mechanism of ncRNA in hemophilia A.