Regulation of microRNAs by natural compounds: Implications for cancer therapy

Abstract

MicroRNAs (miRNAs) are evolutionarily conserved short (19–22 nucleotides) noncoding RNA sequences that bind to target mRNAs, leading to their degradation or inhibition of translation. They have received a lot of attention in recent years as fi ne regulators of gene expression thus in fluencing many biological processes including the development and progression of cancers. Many miRNAs with a role in cancer including invasion and metastasis as well as those having tumor suppressor activities have been characterized. Expression profiling of miRNAs classi fies cancers and even serves to predict prognosis. Aberrations in miRNA expression affect that of their target proteins eventually altering the chemosensitivity of tumor cells. Targeting miRNAs for cancer therapy is thus an emerging fi eld for treatment optimization aiming to inhibit proliferation of cancer cells and/or to increase their sensitivity to conventional chemotherapy by inducing apoptosis. Natural compounds and dietary constituents such as curcumin, epigallocatechin-3-gallate, ellagitannin, folates, retinoids and some iso flavones are known to have antiproliferative and/or apoptotic effects in cancer cells and have been shown to modulate the miRNA expression pro files. However, detailed mechanisms as to how curcumin or other natural compounds regulate miRNAs are not known. The natural compounds are relatively non-toxic and their combination with conventional chemotherapy could be a novel and safer approach to eliminate the resistant cancer stem cells or those undergoing epithelial to mesenchymal transition (EMT) and realize the ultimate goal of improving the drug sensitivity (Kawasaki et al. 2008; Kakarala et al. 2010; Tang et al. 2010a). Deep understanding on the mechanisms of miRNA regulation by natural compounds would offer promising hopes to overcome anticancer drug resistance.