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miR-200c: a versatile watchdog in cancer progression, EMT, and drug resistance

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Abstract

MicroRNAs (miRNAs) are 20–22-nucleotide small endogenous non-coding RNAs which regulate gene expression at post-transcriptional level. In the last two decades, identification of almost 2600 miRNAs in human and their potential to be modulated opened a new avenue to target almost all hallmarks of cancer. miRNAs have been classified as tumor suppressors or oncogenes depending on the phenotype they induce, the targets they modulate, and the tissue where they function. miR-200c, an illustrious tumor suppressor, is one of the highly studied miRNAs in terms of development, stemness, proliferation, epithelial-mesenchymal transition (EMT), therapy resistance, and metastasis. In this review, we first focus on the regulation of miR-200c expression and its role in regulating EMT in a ZEB1/E-cadherin axis-dependent and ZEB1/E-cadherin axis-independent manner. We then describe the role of miR-200c in therapy resistance in terms of multidrug resistance, chemoresistance, targeted therapy resistance, and radiotherapy resistance in various cancer types. We highlight the importance of miR-200c at the intersection of EMT and chemoresistance. Furthermore, we show how miR-200c coordinates several important signaling cascades such as TGF-β signaling, PI3K/Akt signaling, Notch signaling, VEGF signaling, and NF-κB signaling. Finally, we discuss miR-200c as a potential prognostic/diagnostic biomarker in several diseases, but mainly focusing on cancer and its potential application in future therapeutics.

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Acknowledgments and funding information

We would like to thank Suhail Ansari and Rasmi Mishra for their critical reading of the manuscript and valuable suggestions. This work is, in part, supported by the European Molecular Biology Organization (EMBO) Installation Grant (Grant No. 2791) and TUBITAK (Grant No. 214S104).

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  1. Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, B Building SB-247, 06800, Ankara, Turkey

    Merve Mutlu, Umar Raza, Özge Saatci, Erol Eyüpoğlu, Emre Yurdusev & Özgür Şahin

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  1. Merve Mutlu
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Mutlu, M., Raza, U., Saatci, Ö. et al. miR-200c: a versatile watchdog in cancer progression, EMT, and drug resistance. J Mol Med 94, 629–644 (2016). https://doi.org/10.1007/s00109-016-1420-5

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