摘要
MicroRNA(miRNA)是一种包含18~22个核苷酸单链的非编码小RNA,通过与靶基因的3’-非编码区相互作用而调控基因的表达。MicroRNA-148/152家族包括microRNA-148a(miR-148a),microRNA-148b(miR-148b)和microRNA-152(miR-152),其在不同的组织中有不同的表达。一些研究已经证实miR-148/152家族成员在许多肿瘤性疾病中存在差异表达,并通过调控靶基因的表达而发挥着调节肿瘤生长、增殖、凋亡、血管新生以及对药物敏感性等多种生物学功能。MiR-148/152家族成员的表达受其本身Cp G岛甲基化的调控,并能靶向作用于其下游的靶基因-DNA甲基转移酶(DNMT1/3b),因此DNMT1/3b反向局限于miR-148a/152的表达。DNMT1/3b过表达促进MiR-148/152家族Cp G岛甲基化,阻碍其发挥作用,导致DNMT1/3b进一步升高。因此,MiR-148/152-DNM T1/3b循环可能是存在的。表观遗传学的异常,尤其是启动子高甲基化在血液恶性肿瘤的发生、发展过程中起重要作用。去甲基化治疗已成为治疗恶性血液病的又一重要途径。本文对miR-148/152家族在血液恶性肿瘤中的表达做一总结,旨在阐述DNA甲基化修饰与micro-RNA在血液肿瘤研究中的重要提示意义。
MicroRNAs(miRNAs) are small noncoding RNA molecules containing 18-22 nucleotides that regulate gene expression through imperfect interactions with sequences in the 3’-untranslated region( 3’-UTR) of target genes.M embers of the microRNA-148 /152( miR-148 /152) family,which include microRNA-148a( miR-148a),microRNA-148b( miR-148b) and microRNA-152( miR-152),are of great importance in the development of some tumor diseases.Several studies have demonstrated that members of the miR-148 /152 family were expressed differently in many kinds of malignancies,and they play a variety of biological functions,such as regulating tumor growth,proliferation,apoptosis,angiogenesis,and sensitivity to drugs through regulating the expression of target genes. The miR-148 /152 family is regulated by methylation of their CPG islands,which reduce the expression of miR-148 /152 family members. Interaction has been observed between DNA methylation and miR-148 /152 family members through their target gene: DNM T1 /3b,an important gene for DNA methylation. So expressions of DNM T1 /3b are inversely restricted to the expression level of miR-148 a /152. This might result in overexpression of DNM T1 /3b,promoting DNA methylation. And then,more DNM T1 /3b can be expressed. A novel miR-148 a /152-DNM T1 /3b regulatory circuit might exist in tumors. Epigenetic abnormalities,especially high methylation of promoter play an important role in occurrence and development of hematological malignancies. Demethylation treatment has become another important way for the treatment. This article summarizes the expression of miR-148 /152 family in hematological malignancies,aiming at expounding the signicance of relationship between DNA methylation modification and microRNA.
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2015年第4期1173-1178,共6页
Journal of Experimental Hematology
基金
辽宁省科技厅科学技术计划项目(2013021031)
