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MicroRNAs regulating SOX2 in cancer progression and therapy response

Published online by Cambridge University Press:  29 September 2021

Sepideh Mirzaei
Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran
Hamidreza Saebfar
Asu Vanda Gene Industrial Research Company, Tehran, Iran
Mohammad Hossein Gholami
Faculty of Veterinary Medicine, Kazerun Branch, Islamic Azad University, Kazerun, Iran
Farid Hashemi
Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
Ali Zarrabi
Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla34956, Istanbul, Turkey
Amirhossein Zabolian
Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Maliheh Entezari
Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Kiavash Hushmandi
Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
Saeed Samarghandian
Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
Amir Reza Aref*
Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA Department of Translational Sciences, Xsphera Biosciences Inc., Boston, MA, USA
Milad Ashrafizadeh
Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Üniversite Caddesi No. 27, Orhanlı, Tuzla34956Istanbul, Turkey
Haroon Khan*
Department of Pharmacy, Abdul Wali Khan University, Mardan23200, Pakistan
Author for correspondence: Amir Reza Aref, Haroon Khan, E-mail:,
Author for correspondence: Amir Reza Aref, Haroon Khan, E-mail:,


The proliferation, metastasis and therapy response of tumour cells are tightly regulated by interaction among various signalling networks. The microRNAs (miRNAs) can bind to 3′-UTR of mRNA and down-regulate expression of target gene. The miRNAs target various molecular pathways in regulating biological events such as apoptosis, differentiation, angiogenesis and migration. The aberrant expression of miRNAs occurs in cancers and they have both tumour-suppressor and tumour-promoting functions. On the contrary, SOX proteins are capable of binding to DNA and regulating gene expression. SOX2 is a well-known member of SOX family that its overexpression in different cancers to ensure progression and stemness. The present review focuses on modulatory impact of miRNAs on SOX2 in affecting growth, migration and therapy response of cancers. The lncRNAs and circRNAs can function as upstream mediators of miRNA/SOX2 axis in cancers. In addition, NF-κB, TNF-α and SOX17 are among other molecular pathways regulating miRNA/SOX2 axis in cancer. Noteworthy, anti-cancer compounds including bufalin and ovatodiolide are suggested to regulate miRNA/SOX2 axis in cancers. The translation of current findings to clinical course can pave the way to effective treatment of cancer patients and improve their prognosis.

Copyright © The Author(s), 2021. Published by Cambridge University Press

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