Cell Death Pathways and Viruses: Role of Micrornas Publisher



Sadri Nahand J¹ ; Shojaie L² ; Akhlagh SA³ ; Ebrahimi MS⁴ ; Mirzaei HR⁵ ; Bannazadeh Baghi H⁶ ; Mahjoubintehran M⁷ ; Rezaei N^{5, 8, 9} ; Hamblin MR^{10, 11} ; Tajiknia V¹² ; Rahimian N¹³ ; Mirzaei H¹⁴ Show Affiliations
Source: Molecular Therapy Nucleic Acids Published:2021

Abstract

Viral infections lead to the death of more than a million people each year around the world, both directly and indirectly. Viruses interfere with many cell functions, particularly critical pathways for cell death, by affecting various intracellular mediators. MicroRNAs (miRNAs) are a major example of these mediators because they are involved in many (if not most) cellular mechanisms. Virus-regulated miRNAs have been implicated in three cell death pathways, namely, apoptosis, autophagy, and anoikis. Several molecules (e.g., BECN1 and B cell lymphoma 2 [BCL2] family members) are involved in both apoptosis and autophagy, while activation of anoikis leads to cell death similar to apoptosis. These mechanistic similarities suggest that common regulators, including some miRNAs (e.g., miR-21 and miR-192), are involved in different cell death pathways. Because the balance between cell proliferation and cell death is pivotal to the homeostasis of the human body, miRNAs that regulate cell death pathways have drawn much attention from researchers. miR-21 is regulated by several viruses and can affect both apoptosis and anoikis via modulating various targets, such as PDCD4, PTEN, interleukin (IL)-12, Maspin, and Fas-L. miR-34 can be downregulated by viral infection and has different effects on apoptosis, depending on the type of virus and/or host cell. The present review summarizes the existing knowledge on virus-regulated miRNAs involved in the modulation of cell death pathways. Understanding the mechanisms for virus-mediated regulation of cell death pathways could provide valuable information to improve the diagnosis and treatment of many viral diseases. © 2021 The Author(s)