Circular RNAs as promising tools for cancer therapy

Abstract

Introduction: Recent progresses in deep sequencing technologies led to underlying more complexities of the human transcriptome. Circular RNAs (circRNAs) are a new group of regulatory non-coding RNAs that arise from back-splicing process with covalently closed ends. Up to now, different functions were proposed for circRNAs include detaching proteins from their original sub-cellular localization, regulating parental gene expression, RNA-protein interactions and serving as miRNA sponges. Description: In addition, many of the circRNAs have been involved in the pathogenesis of multi-factorial diseases, such as atherosclerosis, neural disorders and lots of cancers. As described above, deregulation of circRNAs may influence cancer- related processes such as proliferative signaling pathways, epithelial-to-mesenchymal transition, angiogenesis, apoptosis and drug resistance and play role in the progression of cancer. So, it would be possible to apply these novel regulators for cancer therapeutic targets through circrNA-miRNA- mRNA network regulating. A probable therapeutic manner may be to target the unique back-splice junction of oncogenic circRNAs by exogenous delivery of complementary small interfering RNA (si RNA). Also, to induce the expression of tumor-suppressor circRNA, exogenous expression can be applied through extracellular vesicles (EVs), such as exosomes and nanoparticles. On the other hands, high cellular stability and capacity of circRNA to sponge miRNA and proteins let us to serve circRNA as a proper vehicle for delivery of therapeutics. Up to now, several studies assessed these approaches to suppress tumor cells of gastric cancer, leukemia, thyroid cancer, bladder cancer, lung cancer and hepatocellular carcinoma. Discussion and conclusion: So far, circRNA therapy is in the beginning and distinct correlation between many differentially expressed circRNAs and tumorigenesis not fully understood. Furthermore, there has been no preclinical evidence where circRNAs alone have been used as targets or therapeutic vectors to treat cancers. So, deeper understanding of circRNA biology is required for future perspectives in terms of molecular therapy of cancer.