Modulation of miRNAs by Natural Agents: Nature’s way of dealing with cancer

Abstract

Accumulating lines of evidence have revealed that microRNAs (miRNAs) play critical roles in many biological processes, such as carcinogenesis, angiogenesis, programmed cell death, cell proliferation, invasion, migration, and differentiation. They act either as tumor suppressors or oncogenes, and alteration in their expression patterns has been linked to onset, progression and chemoresistance of various cancers. Moreover, miRNAs are also crucial for the regulation of cancer stem cells (CSCs) self-renewal and proliferation as well as control of Epithelial-to-Mesenchymal Transition (EMT) of cancer cells. Therefore, exploitation of miRNAs as targets for cancer prevention and therapy could be a promising approach. Several experimental and epidemiologic studies have shown that dietary intake of natural agents such as baicalin, ginsenoside, curcumin, resveratrol, genistein, epigallocatechin-3-gallate (EGCG), indole-3-carbinol, 3,3΄-diindolylmethane (DIM) including antioxidants among others is inversely associated with the risk for cancer, demonstrating the inhibitory effects of natural agents on carcinogenesis. Additionally, the anticancer agents from natural agents have been found to inhibit the development and progression of cancer through the regulation of various cancer processes such as apoptosis, cell cycle regulation, differentiation, inflammation, angiogenesis, and metastasis. Importantly, natural agents could significantly impact the expression of tumor-suppressor and oncogenic miRNAs, regulate cellular signaling networks, inhibit cancer cell growth and cancer stem cell self-renewal. This is important for the normalization of altered cellular signaling mechanisms in cancer cells. This postulates a much broader use of natural agents in the prevention and/or treatment of various cancers in combination with conventional chemotherapeutics. However, more in vitro mechanistic experiments, in vivo animal studies, and clinical trials are warranted to realize the true value of natural agents in the prevention and/or treatment of cancer. Herein, we provide an overview of natural agents' modulation of miRNA expression as well as highlight the significance of these observations as potential new strategies in cancer therapies. This review will help us to understand how miRNAs are regulated by natural agents and also help in the development of effective and secure natural agents for therapeutic purposes.