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[微小RNA-148/152家族在血液系统恶性肿瘤中的表达]

[Expression of MicroRNA-148/152 Family in the Hematological Malignancies].

作者信息

Wang Xiao-Xue, Wang Yue, Wang Ping-Ping, Li Yan

机构信息

Department of Hematology, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.

Department of Hematology, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China. E-mail:

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2015 Aug;23(4):1173-8. doi: 10.7534/j.issn.1009-2137.2015.04.052.

Abstract

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. Members 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: DNMT1/3b, an important gene for DNA methylation. So expressions of DNMT1/3b are inversely restricted to the expression level of miR-148a/152. This might result in overexpression of DNMT1/3b, promoting DNA methylation. And then, more DNMT1/3b can be expressed. A novel miR-148a/152-DNMT1/3b 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.

摘要

微小RNA(miRNA)是一类含有18 - 22个核苷酸的小型非编码RNA分子,它们通过与靶基因3'非翻译区(3'-UTR)序列的不完全相互作用来调节基因表达。微小RNA - 148/152(miR - 148/152)家族成员,包括微小RNA - 148a(miR - 148a)、微小RNA - 148b(miR - 148b)和微小RNA - 152(miR - 152),在某些肿瘤疾病的发生发展中具有重要意义。多项研究表明,miR - 148/152家族成员在多种恶性肿瘤中表达存在差异,并且它们发挥多种生物学功能,例如通过调节靶基因的表达来调控肿瘤生长、增殖、凋亡、血管生成以及对药物的敏感性。miR - 148/152家族受其CPG岛甲基化调控,这会降低miR - 148/152家族成员的表达。通过它们的靶基因:DNA甲基转移酶1/3b(DNMT1/3b,DNA甲基化的一个重要基因),观察到了DNA甲基化与miR - 148/152家族成员之间的相互作用。所以DNMT1/3b的表达与miR - 148a/152的表达水平呈负相关。这可能导致DNMT1/3b的过表达,促进DNA甲基化。进而,可以表达更多的DNMT1/3b。肿瘤中可能存在一种新的miR - 148a/152 - DNMT1/3b调控回路。表观遗传异常,尤其是启动子的高甲基化在血液系统恶性肿瘤的发生发展中起重要作用。去甲基化治疗已成为另一种重要的治疗方式。本文总结了miR - 148/152家族在血液系统恶性肿瘤中的表达情况,旨在阐述DNA甲基化修饰与微小RNA之间关系的意义。

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