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Review
. 2009 Mar 15;8(6):843-52.
doi: 10.4161/cc.8.6.7907. Epub 2009 Mar 22.

Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression

Marcus E Peter  1
Affiliations
Review

Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression

Marcus E Peter. Cell Cycle. .

Abstract

Micro (mi)RNAs are emerging as important regulators of cellular differentiation, their importance underscored by the fact that they are often dysregulated during carcinogenesis. Two evolutionary conserved families, let-7 and miR-200, regulate key differentiation processes during development. Loss of let-7 in cancer results in reverse embryogenesis and dedifferentiation, and miR-200 has been identified as a powerful regulator of epithelial-to-mesenchymal transition (EMT). Recent findings have connected let-7 with stem cell maintenance and point at a connection between EMT and stem cell formation. A part of tumor progression can be viewed as a continuum of progressive dedifferentiation (EMT) with a cell at the endpoint that has stem cell-like properties. I propose that steps of this process are driven by specific changes in the expression of let-7 and miR-200 family members.

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Figures

Figure 1
Figure 1
Expression of let-7 and miR-200 Is Regulated by Negative Feedback Loops. (A) Regulation of let-7 processing by the let-7 targets Lin28/Lin28B. (B) Regulation of miR-200 expression by the miR-200 targets ZEB1/ZEB2. For details see text.
Figure 2
Figure 2
Model to Illustrate how let-7 and miR-200 Could Each Contribute to Tumor Progression, One by Controlling let-7 Regulated Oncofetal Genes (LOGs) and the Other by Regulating EMT and Metastasis. Crosstalk exists between the pathways that regulate reverse embryogenesis and EMT. For details see text.
Figure 3
Figure 3
Deregulation of let-7 and miR-200 during carcinogenesis.
See this image and copyright information in PMC

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