MicroRNA Therapeutics: The Emerging Anticancer Strategies
Chakresh K. Jain, Aman Gupta, Nidhi Dogra, Vipul S. Kumar, Gulshan Wadhwa and Sanjeev K. Sharma
Affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector-62, NOIDA, U.P. (India).
Keywords: Anticancer, drosha, dicer, exportin-5, microRNAs, RNA-induced silencing complex (RISC), RNA interference,
The genetic alterations and aberrant miRNA expression profiles have been identified as important events behind
the emergence of cancer. This knowledge triggers the use of miRNA therapeutics as an anticancer strategy. Basically,
MicroRNAs (miRNAs) are approximately 22-nucleotide long, endogenous non-protein-coding RNA molecules
which function as important regulatory molecules that regulate gene and protein expression through the RNA interference
(RNAi) machinery. Transcription of these molecules by RNA polymerases II and III, resulting in the generation of precursor
microRNAs that undergo a series of cleavage events, consequently, generate the mature microRNA. The biogenesis
pathway is mediated by the two important cleavage events such as nuclear and cytoplasmic. The regulatory functions of
microRNAs are accomplished through the RNA-induced silencing complex (RISC), leading to translational repression
and hence, regulate the gene expression. The current progress in the development of strategies for miRNA-based anticancer
therapies is due to its involvement in cellular, developmental and biological processes including regulation in cancer
cell and modulation by various cancer chemoprophylaxis agents. Although miRNA therapeutics have been found to
suppress gene expression effectively as compared to anti-sense oligonucleotide strategies, but it is bound with some limitations
viz. identification of tissue specific miRNA, biological instability, off-target effects and delivery in the cell system.
Up to certain extent, these hurdles have been resolved by chemical modifications using cholesterol conjugation, morpholinos,
cationic lipids and cationic nanoparticles. Still more research is needed to understand the mechanism of action
for better miRNA therapeutics. The paper discusses the potential miRNA therapeutics and diagnostic applications for cancer
prevention, based on recent patents and their analysis.
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