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

Mutlu, M.
Raza, U.
Saatci, Ö.
Eyüpoğlu, E.
Yurdusev, E.
Şahin, Ö.
Source Title
Journal of Molecular Medicine
Print ISSN
Electronic ISSN
Springer Verlag
629 - 644
Journal Title
Journal ISSN
Volume Title

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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Book Title
Biomarker, Cell signaling, Drug resistance, Epithelial-mesenchymal transition (EMT), miR-200c, TGF-β, ZEB1/2, Immunoglobulin enhancer binding protein, MicroRNA 200c, Phosphatidylinositol 3 kinase, Transcription factor ZEB1, Transforming growth factor beta, Uvomorulin, Vasculotropin, Antineoplastic agent, Cadherin, CDH1 protein, human, MicroRNA, MIRN200 microRNA, human, Transcription factor ZEB1, Transforming growth factor beta, ZEB1 protein, human, ZEB2 protein, human, Zinc finger E box binding homeobox 2, Cancer growth, Cancer resistance, Chemotherapy resistance, Epithelial mesenchymal transition, Gene expression, Guard dog, Multidrug resistance, Nonhuman, Radiotherapy resistance, Review, Therapy resistance, Animal, Cell transformation, Disease exacerbation, Drug resistance, Epithelial mesenchymal transition, Gene expression regulation, Genetics, Human, Metabolism, Neoplasm, Pathology, Signal transduction, Animals, Antineoplastic Agents, Cadherins, Cell Transformation, Neoplastic, Disease Progression, Drug Resistance, Neoplasm, Epithelial-Mesenchymal Transition, Gene Expression Regulation, Neoplastic, Humans, MicroRNAs, Neoplasms, Signal Transduction, Transforming Growth Factor beta, Zinc Finger E-box Binding Homeobox 2, Zinc Finger E-box-Binding Homeobox 1
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