Nuclear export mediated regulation of microRNAs: potential target for drug intervention.
Nuclear export mediated regulation of microRNAs: potential target for drug intervention.
复制标题
DOI：
10.2174/1389450111314100002
复制
发表时间：
2013-09
影响因子：
3.2
通讯作者：
Azmi AS
中科院分区：
文献类型：
--
作者：
Muqbil I;Bao B;Abou-Samra AB;Mohammad RM;Azmi AS
microRNA（miRNAs）是一类短的非编码RNA，参与调控无数基因的表达。已发现它们的异常表达与包括癌症在内的许多疾病的病理学有关。存在开发针对不同疾病尤其是癌症的miRNA靶向治疗剂的驱动力。然而，控制这些短的非编码RNA并不像最初想象的那样简单。这是鉴于最近发现miRNA在多个水平上受到表观遗传调控。输出蛋白5（XPO 5）核输出介导的miRNA调控是这样一种重要的表观遗传机制。XPO 5负责将前体miRNA通过核膜输出到细胞质，因此是miRNA生物合成的关键步骤。许多研究表明，miRNA生物合成途径组分的变化，特别是XPO 5的异常表达，会增加患癌症的风险。除了XPO 5外，Exportin 1蛋白（XPO 1）或染色体区域维持1（CRM 1）也可以携带miRNA输出功能。这些发现得到了通路分析的支持，这些通路分析揭示了某些miRNA作为CRM1的直接相互作用伙伴。深入了解miRNA输出介导的调控机制对于成功设计临床可行的治疗方法非常重要。在这篇综述中，我们描述了目前对miRNA核转运介导的调节机制的认识，并提出了选择性阻断癌症中这一重要机制的策略。
MicroRNAs (miRNAs) are short non-coding RNAs that have been recognized to regulate the expression of uncountable number of genes. Their aberrant expression has been found to be linked to the pathology of many diseases including cancer. There is a drive to develop miRNA targeted therapeutics for different diseases especially cancer. Nevertheless, reining in these short non-coding RNAs is not as straightforward as originally thought. This is in view of the recent discoveries that miRNAs are under epigenetic regulations at multiple levels. Exportin 5 protein (XPO5) nuclear export mediated regulation of miRNAs is one such important epigenetic mechanism. XPO5 is responsible for exporting precursor miRNAs through the nuclear membrane to the cytoplasm, and is thus a critical step in miRNA biogenesis. A number of studies have shown that variations in components of the miRNA biogenesis pathways, particularly the aberrant expression of XPO5, increase the risk of developing cancer. In addition to XPO5, the Exportin 1 protein (XPO1) or chromosome region maintenance 1 (CRM1) can also carry miRNA export function. These findings are supported by pathway analyses that reveal certain miRNAs as direct interaction partners of CRM1. An in depth understanding of miRNA export mediated regulatory mechanisms is important for the successful design of clinically viable therapeutics. In this review, we describe the current knowledge on the mechanisms of miRNA nuclear transport mediated regulation and propose strategies to selectively block this important mechanism in cancer.
登录
查看更多内容
影响因子：
11.4
作者：
Etchin, J.;Sun, Q.;Kentsis, A.;Farmer, A.;Zhang, Z. C.;Sanda, T.;Mansour, M. R.;Barcelo, C.;McCauley, D.;Kauffman, M.;Shacham, S.;Christie, A. L.;Kung, A. L.;Rodig, S. J.;Chook, Y. M.;Look, A. T.
通讯作者：
Look, A. T.
影响因子：
29.4
作者：
Azmi AS;Aboukameel A;Bao B;Sarkar FH;Philip PA;Kauffman M;Shacham S;Mohammad RM
通讯作者：
Mohammad RM
影响因子：
5.7
作者：
Azmi AS;Wang Z;Philip PA;Mohammad RM;Sarkar FH
通讯作者：
Sarkar FH
DOI：
10.1016/1043-4682(92)90029-u
发表时间：
1992-08-01
期刊：
Seminars in cell biology
影响因子：
--
作者：
Izaurralde, E;Mattaj, I W
通讯作者：
Mattaj, I W
影响因子：
64.8
作者：
Eulalio, Ana;Mano, Miguel;Giacca, Mauro
通讯作者：
Giacca, Mauro