Title:miRNA Regulation of Glutathione Homeostasis in Cancer Initiation, Progression and Therapy Resistance
VOLUME: 9 ISSUE: 3
Author(s):Barbara Marengo*, Alessandra Pulliero, Alberto Izzotti and Cinzia Domenicotti
Affiliation:Department of Experimental Medicine, University of Genoa, Genoa, Department of Health Sciences, University of Genoa, Genoa, Department of Experimental Medicine, University of Genoa, Genoa, Department of Experimental Medicine, University of Genoa, Genoa
Keywords:Cancer, chemoresistance, epigenetic mechanisms, glutathione homeostasis, miRNA, reactive oxygen species.
Abstract:Glutathione (GSH) is the most abundant antioxidant that contributes to regulating the cellular
production of Reactive Oxygen Species (ROS) which, maintained at physiological levels, can
exert a function of second messengers in living organisms. In fact, it has been demonstrated that
moderate amounts of ROS can activate the signaling pathways involved in cell growth and proliferation,
while high levels of ROS induce DNA damage leading to cancer development. Therefore, GSH
is a crucial player in the maintenance of redox homeostasis and its metabolism has a role in tumor
initiation, progression, and therapy resistance. Our recent studies demonstrated that neuroblastoma
cells resistant to etoposide, a common chemotherapeutic drug, show a partial monoallelic deletion of
the locus coding for miRNA 15a and 16-1 leading to a loss of these miRNAs and the activation of
GSH-dependent responses. Therefore, the aim of this review is to highlight the role of specific miRNAs
in the modulation of intracellular GSH levels in order to take into consideration the use of modulators
of miRNA expression as a useful strategy to better sensitize tumors to current therapies.
