Role of microRNA/Epithelial-to-Mesenchymal Transition Axis in the Metastasis of Bladder Cancer.

Bladder cancer (BC) is the 11th most common diagnosed cancer, and a number of factors including environmental and genetic ones participate in BC development. Metastasis of BC cells into neighboring and distant tissues significantly reduces overall survival of patients with this life-threatening disorder. Recently, studies have focused on revealing molecular pathways involved in metastasis of BC cells, and in this review, we focus on microRNAs (miRNAs) and their regulatory effect on epithelial-to-mesenchymal transition (EMT) mechanisms that can regulate metastasis. EMT is a vital process for migration of BC cells, and inhibition of this mechanism restricts invasion of BC cells. MiRNAs are endogenous non-coding RNAs with 19-24 nucleotides capable of regulating different cellular events, and EMT is one of them. In BC cells, miRNAs are able to both induce and/or inhibit EMT. For regulation of EMT, miRNAs affect different molecular pathways such as transforming growth factor-beta (TGF-β), Snail, Slug, ZEB1/2, CD44, NSBP1, which are, discussed in detail this review. Besides, miRNA/EMT axis can also be regulated by upstream mediators such as lncRNAs, circRNAs and targeted by diverse anti-tumor agents. These topics are also discussed here to reveal diverse molecular pathways involved in migration of BC cells and strategies to target them to develop effective therapeutics.

Biomolecules. 2020 Aug 07*** epublish ***

Milad Ashrafizadeh, Kiavash Hushmandi, Mehrdad Hashemi, Mohammad Esmaeil Akbari, Peter Kubatka, Mehdi Raei, Lenka Koklesova, Md Shahinozzaman, Reza Mohammadinejad, Masoud Najafi, Gautam Sethi, Alan Prem Kumar, Ali Zarrabi

Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz 5166616471, Iran., Department of Food Hygiene and Quality Control, Division of Epidemiology & Zoonoses, Faculty of Veterinary Medicine, University of Tehran, Tehran 1419963114, Iran., Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran 1916893813, Iran., Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran 1989934148, Iran., Department of Medical Biology and Division of Oncology-Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia., Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran 1435916471, Iran., Department of Obstetrics and Gynecology, Martin University Hospital and Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia., Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742, USA., Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman 55877577, Iran., Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah 6715847141, Iran., Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore., Sabanci University Nanotechnology Research and Application Center (SUNUM), Sabanci University, Tuzla, Istanbul 34956, Turkey.