Title:Targeting CSCs in Tumor Microenvironment: The Potential Role of ROS-Associated miRNAs in Tumor Aggressiveness
Volume: 9
Issue: 1
Author(s): Bin Bao, Asfar S. Azmi, Yiwei Li, Aamir Ahmad, Shadan Ali, Sanjeev Banerjee, Dejuan Kong and Fazlul H. Sarkar
Affiliation:
Keywords:
ROS, CSCs, EMT, hypoxia, miRNAs, genistein.
Abstract: Reactive oxygen species (ROS) have been widely considered as critical cellular signaling molecules involving
in various biological processes such as cell growth, differentiation, proliferation, apoptosis, and angiogenesis. The homeostasis
of ROS is critical to maintain normal biological processes. Increased production of ROS, namely oxidative stress,
due to either endogenous or exogenous sources causes irreversible damage of bio-molecules such as DNA, proteins, lipids,
and sugars, leading to genomic instability, genetic mutation, and altered gene expression, eventually contributing to
tumorigenesis. A great amount of experimental studies in vitro and in vivo have produced solid evidence supporting that
oxidative stress is strongly associated with increased tumor cell growth, treatment resistance, and metastasis, and all of
which contribute to tumor aggressiveness. More recently, the data have indicated that altered production of ROS is also
associated with cancer stem cells (CSCs), epithelial-to-mesenchymal transition (EMT), and hypoxia, the most common
features or phenomena in tumorigenesis and tumor progression. However, the exact mechanism by which ROS is involved
in the regulation of CSC and EMT characteristics as well as hypoxia- and, especially, HIF-mediated pathways is not well
known. Emerging evidence suggests the role of miRNAs in tumorigenesis and progression of human tumors. Recently,
the data have indicated that altered productions of ROS are associated with deregulated expression of miRNAs, suggesting
their potential roles in the regulation of ROS production. Therefore, targeting ROS mediated through the deregulation
of miRNAs by novel approaches or by naturally occurring anti-oxidant agents such as genistein could provide a new
therapeutic approach for the prevention and/or treatment of human malignancies. In this article, we will discuss the potential
role of miRNAs in the regulation of ROS production during tumorigenesis. Finally, we will discuss the role of genistein,
as a potent anti-tumor agent in the regulation of ROS production during tumorigenesis and tumor development.