miR-200c: a versatile watchdog in cancer progression, EMT, and drug resistance.
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.
Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, B Building SB-247, 06800, Ankara, Turkey.
Merve
M
Mutlu
Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, B Building SB-247, 06800, Ankara, Turkey.
Umar
U
Raza
Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, B Building SB-247, 06800, Ankara, Turkey.
Özge
Ö
Saatci
Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, B Building SB-247, 06800, Ankara, Turkey.
Erol
E
Eyüpoğlu
Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, B Building SB-247, 06800, Ankara, Turkey.
Emre
E
Yurdusev
Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, B Building SB-247, 06800, Ankara, Turkey. sahinozgur@gmail.com.
Özgür
Ö
Şahin
D000818:Animals; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D000074165:Zinc Finger E-box Binding Homeobox 2 / Q000235:genetics / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D000970:Antineoplastic Agents; C513384:CDH1 protein, human; D015820:Cadherins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D016212:Transforming Growth Factor beta; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
Biomarker; Cell signaling; Drug resistance; Epithelial-mesenchymal transition (EMT); TGF-β; ZEB1/2; miR-200c