Functional Role of the microRNA-200 Family in Breast Morphogenesis and Neoplasia.
Functional Role of the microRNA-200 Family in Breast Morphogenesis and Neoplasia.
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DOI：
10.3390/genes5030804
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发表时间：
2014-09-11
期刊：
影响因子：
3.5
通讯作者：
Gudjonsson T
中科院分区：
文献类型：
--
作者：
Hilmarsdottir B;Briem E;Bergthorsson JT;Magnusson MK;Gudjonsson T
分支上皮形态发生与上皮-间质转化（EMT）密切相关，EMT是正常发育和癌症进展中的重要过程。miR-200家族通过与ZEB 1和ZEB 2转录因子的负反馈环调节上皮形态发生和EMT。miR-200抑制ZEB 1/2 mRNA的表达，这反过来可以下调miR-200家族，进一步导致E-钙粘蛋白的下调和间充质表型的诱导。最近的研究表明，miR-200基因在妊娠晚期和哺乳期高表达，从而表明这些miR对乳腺上皮的形态发生和分化很重要。miR-200基因已被深入研究与乳腺癌进展和转移的关系，其中已显示miR-200成员在EMT表型突出的基底样乳腺癌中下调。越来越多的证据表明miR-200家族在远端乳腺转移中上调，表明这些miR通过诱导间充质向上皮转化对转移性乳腺癌细胞的定殖很重要。miR-200在原发性和转移性乳腺癌中的双重作用对未来的治疗干预很有意义，因此更详细地了解其作用和相互作用的伙伴非常重要。
Branching epithelial morphogenesis is closely linked to epithelial-to-mesenchymal transition (EMT), a process important in normal development and cancer progression. The miR-200 family regulates epithelial morphogenesis and EMT through a negative feedback loop with the ZEB1 and ZEB2 transcription factors. miR-200 inhibits expression of ZEB1/2 mRNA, which in turn can down-regulate the miR-200 family that further results in down-regulation of E-cadherin and induction of a mesenchymal phenotype. Recent studies show that the expression of miR-200 genes is high during late pregnancy and lactation, thereby indicating that these miRs are important for breast epithelial morphogenesis and differentiation. miR-200 genes have been studied intensively in relation to breast cancer progression and metastasis, where it has been shown that miR-200 members are down-regulated in basal-like breast cancer where the EMT phenotype is prominent. There is growing evidence that the miR-200 family is up-regulated in distal breast metastasis indicating that these miRs are important for colonization of metastatic breast cancer cells through induction of mesenchymal to epithelial transition. The dual role of miR-200 in primary and metastatic breast cancer is of interest for future therapeutic interventions, making it important to understand its role and interacting partners in more detail.
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影响因子：
4.6
作者：
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通讯作者：
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