MicroRNAs and Their Influence on the ZEB Family: Mechanistic Aspects and Therapeutic Applications in Cancer Therapy
Milad Ashrafizadeh,
Hui Li Ang,
Ebrahim Rahmani Moghadam,
Shima Mohammadi,
Vahideh Zarrin,
Kiavash Hushmandi,
Saeed Samarghandian,
Ali Zarrabi,
Masoud Najafi,
Reza Mohammadinejad,
Alan Prem Kumar
Affiliations
Milad Ashrafizadeh
Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz 5166616471, Iran
Hui Li Ang
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
Ebrahim Rahmani Moghadam
Department of Anatomical Sciences, School of Medicine, Student Research Committee, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
Shima Mohammadi
General Practitioner, Kerman University of Medical Sciences, Kerman 7616913555, Iran
Vahideh Zarrin
Laboratory for Stem Cell Research, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
Kiavash Hushmandi
Department of Food Hygiene and Quality Control, Division of Epidemiology & Zoonoses, Faculty of Veterinary Medicine, University of Tehran, Tehran 1417414418, Iran
Saeed Samarghandian
Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur 9318614139, Iran
Ali Zarrabi
Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla 34956, Istanbul, Turkey
Masoud Najafi
Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah 6715847141, Iran
Reza Mohammadinejad
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman 7619813159, Iran
Alan Prem Kumar
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
Molecular signaling pathways involved in cancer have been intensively studied due to their crucial role in cancer cell growth and dissemination. Among them, zinc finger E-box binding homeobox-1 (ZEB1) and -2 (ZEB2) are molecules that play vital roles in signaling pathways to ensure the survival of tumor cells, particularly through enhancing cell proliferation, promoting cell migration and invasion, and triggering drug resistance. Importantly, ZEB proteins are regulated by microRNAs (miRs). In this review, we demonstrate the impact that miRs have on cancer therapy, through their targeting of ZEB proteins. MiRs are able to act as onco-suppressor factors and inhibit the malignancy of tumor cells through ZEB1/2 down-regulation. This can lead to an inhibition of epithelial-mesenchymal transition (EMT) mechanism, therefore reducing metastasis. Additionally, miRs are able to inhibit ZEB1/2-mediated drug resistance and immunosuppression. Additionally, we explore the upstream modulators of miRs such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as these regulators can influence the inhibitory effect of miRs on ZEB proteins and cancer progression.
