The miR-200 and miR-221/222 microRNA families: opposing effects on epithelial identity.
The miR-200 and miR-221/222 microRNA families: opposing effects on epithelial identity.
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DOI：
10.1007/s10911-012-9244-6
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发表时间：
2012-03
影响因子：
2.5
通讯作者：
Richer JK
中科院分区：
文献类型：
--
作者：
Howe EN;Cochrane DR;Richer JK
癌变是一个复杂的过程，在这个过程中，细胞经历了遗传和表观遗传的改变。这些变化可以导致肿瘤细胞获得特征，当条件变得不利时，这些特征能够从原始起源位置移动。这些特征包括前后两极的获得，增加的迁移/侵袭，以及对失巢细胞的抵抗，这些都有助于肿瘤在转移过程中的生存。上皮向间充质转化(EMT)构成了癌细胞获得促进肿瘤进展和转移的特征的一种方式。MiR-200和miR-221这两个microRNA家族在影响乳腺癌分化状态的过程中发挥着重要的对立作用。与分化较差的三阴性乳腺癌(TNBCs)相比，这两个家族在管腔A亚型乳腺癌中的表达存在差异，TNBCs表现出指示EMT的标志。MiR-200家族促进高分化的上皮表型，而高miR-221/222导致低分化的间充质样表型。本文就这两个miRNA家族在乳腺肿瘤发生和转移过程中对细胞可塑性产生相反作用的机制(已证实的特定靶点)进行综述。
Carcinogenesis is a complex process during which cells undergo genetic and epigenetic alterations. These changes can lead tumor cells to acquire characteristics that enable movement from the primary site of origin when conditions become unfavorable. Such characteristics include gain of front-rear polarity, increased migration/invasion, and resistance to anoikis, which facilitate tumor survival during metastasis. An epithelial to mesenchymal transition (EMT) constitutes one way that cancer cells can gain traits that promote tumor progression and metastasis. Two microRNA (miRNA) families, the miR-200 and miR-221 families, play crucial opposing roles that affect the differentiation state of breast cancers. These two families are differentially expressed between the luminal A subtype of breast cancer as compared to the less well-differentiated triple negative breast cancers (TNBCs) that exhibit markers indicative of an EMT. The miR-200 family promotes a well-differentiated epithelial phenotype, while high miR-221/222 results in a poorly differentiated, mesenchymal-like phenotype. This review focuses on the mechanisms (specific proven targets) by which these two miRNA families exert opposing effects on cellular plasticity during breast tumorigenesis and metastasis.