Departments of Pathology and Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, 740 HWCRC, 4100 John R Street, Detroit, MI 48201, USA.
Curr Stem Cell Res Ther. 2014 Jan;9(1):22-35. doi: 10.2174/1574888x113089990053.
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.
活性氧（ROS）被广泛认为是参与各种生物学过程的关键细胞信号分子，如细胞生长、分化、增殖、凋亡和血管生成。ROS 的内稳状态对于维持正常的生物学过程至关重要。由于内源性或外源性原因，ROS 的产生增加，即氧化应激，会导致生物分子如 DNA、蛋白质、脂质和糖不可逆的损伤，导致基因组不稳定、基因突变和基因表达改变，最终导致肿瘤发生。大量的体外和体内实验研究提供了确凿的证据，支持氧化应激与肿瘤细胞生长增加、治疗抵抗和转移密切相关，所有这些都有助于肿瘤的侵袭性。最近的数据表明，ROS 的产生改变也与癌症干细胞（CSC）、上皮-间质转化（EMT）和缺氧有关，这些是肿瘤发生和肿瘤进展中最常见的特征或现象。然而，ROS 如何参与调节 CSC 和 EMT 特征以及缺氧和 HIF 介导的途径的具体机制尚不清楚。新出现的证据表明 miRNA 在人类肿瘤的发生和进展中起作用。最近的数据表明，ROS 的产生改变与 miRNA 的表达失调有关，提示它们在调节 ROS 产生中的潜在作用。因此，通过新型方法或天然抗氧化剂如染料木黄酮靶向 ROS 介导的 miRNA 失调可能为预防和/或治疗人类恶性肿瘤提供新的治疗方法。本文将讨论 miRNA 在肿瘤发生过程中调节 ROS 产生的潜在作用。最后，我们将讨论染料木黄酮作为一种有效的抗肿瘤药物在肿瘤发生和发展过程中调节 ROS 产生的作用。
