Title:Emerging Roles for Modulation of microRNA Signatures in Cancer Chemoprevention
Volume: 12
Issue: 6
Author(s): K. Neelakandan, P. Babu and S. Nair
Affiliation:
Keywords:
Cancer chemoprevention, cancer stem cells, drug metabolism, drug target, MicroRNA
, 2’-O-methoxyethyl, 2-acetylaminofluore, 3’untranslated region, ATP-binding cassette, sub-family G
(WHITE), member 2, alpha-fetoprotein, aldehyde dehydrogenase 1 family, member
A1, anti-miRNA oligonucleotides, Benzo[a]pyrene-trans-7, 8-diol-anti9, 10-
epoxide
Abstract: miRNAs are small endogenous non-coding RNAs, approximately 21-nucleotides in length, which are shown to
regulate an array of cellular processes such as differentiation, cell cycle, cell proliferation, apoptosis, and angiogenesis
which are important in cancer. miRNAs can function as both tumor promoters (oncomiRs) or tumor suppressors by their
ability to target numerous biomolecules that are important in carcinogenesis. Aberrant expression of miRNAs is correlated
with the development and progression of tumors, and the reversal of their expression has been shown to modulate the
cancer phenotype suggesting the potential of miRNAs as targets for anti-cancer drugs. Several chemopreventive
phytochemicals like epigallocatechin-3-gallate, curcumin, isoflavones, indole-3-carbinol, resveratrol, and isothiocyanate
have been shown to modulate the expression of numerous miRNAs in cancer cells that lead to either abrogation of tumor
growth or sensitization of cancer cells to chemotherapeutic agents. This review focuses on the putative role(s) of miRNAs
in different aspects of tumorigenesis and at various stages of early drug discovery that makes them a promising class of
drug targets for chemopreventive intervention in cancer. We summarize the current progress in the development of
strategies for miRNA-based anti-cancer therapies. We also explore the modulation of miRNAs by various cancer
chemopreventive agents and the role of miRNAs in drug metabolism. We will discuss the role of miRNAs in cancer stem
cells and epithelial-to-mesenchymal transition; and talk about how modulation of miRNA expression relates to altered
glycosylation patterns in cancer cells. In addition, we consider the role of altered miRNA expression in carcinogenesis
induced by various agents including genotoxic and epigenetic carcinogens. Finally, we will end with a discussion on the
potential involvement of miRNAs in the development of cancer chemoresistance. Taken together, a better understanding
of the complex role(s) of miRNAs in cancer may help in designing better strategies for biomarker discovery or drug
targeting of miRNAs and/or their putative protein targets.
