The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2.

By Sun-Mi Park, A. Gaur, E. Lengyel, Marcus E. Peter. Genes & Development, 2008

2,342 citations recorded by the source corpus.

Cancer progression has similarities with the process of epithelial-to-mesenchymal transition (EMT) found during embryonic development, during which cells down-regulate E-cadherin and up-regulate Vimentin expression. By evaluating the expression of 207 microRNAs (miRNAs) in the 60 cell lines of the drug screening panel maintained by the Nation Cancer Institute, we identified the miR-200 miRNA family as an extraordinary marker for cells that express E-cadherin but lack expression of Vimentin. These findings were extended to primary ovarian cancer specimens. miR-200 was found to directly target the mRNA of the E-cadherin transcriptional repressors ZEB1 (TCF8/deltaEF1) and ZEB2 (SMAD-interacting protein 1 [SIP1]/ZFXH1B). Ectopic expression of miR-200 caused up-regulation of E-cadherin in cancer cell lines and reduced their motility. Conversely, inhibition of miR-200 reduced E-cadherin expression, increased expression of Vimentin, and induced EMT. Our data identify miR-200 as a powerful marker and determining factor of the epithelial phenotype of cancer cells.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6fc5b54fa1c38cb1164b1a119c76174d4a909659

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Citations in the corpus

MicroRNA-155 Is Regulated by the Transforming Growth Factor β/Smad Pathway and Contributes to Epithelial Cell Plasticity by Targeting RhoA (2008, background): “Recent reports have indicated the importance of downregulation for miR-200 family miRNAs during TGF- -induced EMT (2, 12, 22, 36).”
Targeting Epithelial–Mesenchymal Transition (EMT) to Overcome Drug Resistance in Cancer (2016, background): “Several transcription factors have been identified as master regulators of EMT, including SNAIL factors (SNAI1, also known as Snail and SNAI2, also known as Slug), bHLH factors (E12 and E47, TWIST1 and TWIST2) and ZEB factors (ZEB1 and ZEB2) [7].”
Uncovering Prognosis-Related Genes and Pathways by Multi-Omics Analysis in Lung Cancer (2020, background): “Additionally, miR-200 families are well-known miRNAs that regulate Wnt/β-catenin signaling [34] and also directly regulate EMT by targeting transcriptional repressors of ZEB1 and ZEB2, which regulate CDH1 expression [42,43].”
Transcriptional regulation of cell polarity in EMT and cancer (2008, background): “…is a tight correlation between the expression of the miR200 RNAs and E-cadherin in a panel of 60 human carcinoma cells of the National Cancer Institute (NCI60), indicating that the miR-200 family may be a strong marker and determinant of the epithelial phenotype in cancer cells (Park et al., 2008).”
MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy (2011, neutral): “Screens for miRNAs that are downregulated during the epithelial to mesenchymal transition (EMT) have identified five members of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141 and mir-429”
Implications of the Hybrid Epithelial/Mesenchymal Phenotype in Metastasis (2015, background): “These components form two interlinked mutually inhibitory feedback loops – miR-34/SNAIL and miR-200/ZEB (26–28), such that EMT-inducing signals such as TGF β , EGF, HGF, and Notch activate ZEB and SNAIL, and p53 activates miR-200 and miR-34 (3) ( Figure 1B ).”
MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. (2012, neutral): “However, miRNA regulation can also be transmitted by transcription factors via an integrated regulatory loop (49).”
MicroRNAs in development and disease. (2011, background): “On the other hand, downregulation of the miR-200 family members directly correlates with the expression of E-cadherin in primary serous papillary OC, as it has been shown to directly inhibit the expression of E-cadherin’s repressors ZEB1 and ZEB2 (472).”
MicroRNAs and cancer: short RNAs go a long way. (2009, background): “Members of the miR-200 family of miRNAs target the ZEB transcription factors, known inducers of the EMT, and thus reduce cellular migration and invasiveness (Gregory et al., 2008; Park et al., 2008).”
Epithelial–mesenchymal transition in tumor metastasis (2016, methodology): “Published by FEBS Press and John Wiley & Sons Ltd. et al., 2008; Gregory et al., 2008; Korpal et al., 2008; Park et al., 2008).”
Adherens junction: molecular architecture and regulation. (2009, positive): “These microRNAs act on E-cadherin transcriptional repressors ZEB1/dEF1 and ZEB2/SIP1, and thereby regulate EMT (Gregory et al. 2008; Park et al. 2008).”
MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death (2008, background): “Its activity was found to be mainly mediated through targeting two E-box-binding E-cadherin repressors, ZEB1 and ZEB2 (Gregory et al., 2008; Park et al., 2008).”