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Role of microRNA in epithelial to mesenchymal transition and metastasis and clinical perspectives

Authors Díaz-López A, Moreno-Bueno G, Cano A

Received 14 December 2013

Accepted for publication 9 February 2014

Published 25 April 2014 Volume 2014:6 Pages 205—216

DOI https://doi.org/10.2147/CMAR.S38156

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3


Antonio Díaz-López,1 Gema Moreno-Bueno,1,2 Amparo Cano1

1Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid, Instituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM), IdiPAZ, Madrid, Spain; 2Fundación MDAnderson Internacional, Madrid, Spain

Abstract: The microRNAs (miRNAs) are a class of small, 20–22 nucleotides in length, endogenously expressed noncoding RNAs that regulate multiple targets posttranscriptionally. Interestingly, miRNAs have emerged as regulators of most physiological and pathological processes, including metastatic tumor progression, in part by controlling a reversible process called epithelial-to-mesenchymal transition (EMT). The activation of EMT increases the migratory and invasive properties fundamental for tumor cell spread while activation of the reverse mesenchymal-to-epithelial transition is required for metastasis outgrowth. The EMT triggering leads to the activation of a core of transcription factors (EMT-TFs) – SNAIL1/SNAIL2, bHLH (E47, E2-2, and TWIST1/TWIST2), and ZEB1/ZEB2 – that act as E-cadherin repressors and, ultimately, coordinate EMT. Recent evidence indicates that several miRNAs regulate the expression of EMT-TFs or EMT-activating signaling pathways. Interestingly, some miRNAs and EMT-TFs form tightly interconnected negative feedback loops that control epithelial cell plasticity, providing self-reinforcing signals and robustness to maintain the epithelial or mesenchymal cell status. Among the most significant feedback loops, we focus on the ZEB/miR-200 and the SNAIL1/miR-34 networks that hold a clear impact in the regulation of the epithelial-mesenchymal state. Recent insights into the p53 modulation of the EMT-TF/miRNA loops and epigenetic regulatory mechanisms in the context of metastasis dissemination will also be discussed. Understanding the regulation of EMT by miRNAs opens new avenues for the diagnosis and prognosis of tumors and identifies potential therapeutic targets that might help to negatively impact on metastasis dissemination and increasing patient survival.

Keywords: EMT, MET, microRNAs, cancer, metastasis

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