miRNA Antagonists: a new strategy to cancer and other diseases treatment

As more information gathered from individual miRNAs in recent years, their roles in oncogenesis, progression and suppression in some cancers as well as their involvement in some other diseases, like autoimmune and cardiovascular have been revealed. These cancers are the results of miRNA dysregulation, particularly they are upregulated and then they suppress tumor suppressor genes that leads to tumorization. In this review, we reviewed the latest studies in the miRNA Antagonist development to cancer treatment. In recent years some treatment for these disorders based on miRNA therapy was emerged like miRNA Antagonism and miRNA mimics. A miRNA antagonist is the using of modified nucleotides sequences that has a complementary region to upregulated miRNAs. These nucleotide sequences called anti-miRNA, Antagomir, miRNA sponges and miRNA masks. The first developed anti-miRs target mir-122 in the liver. Locked Nucleic Acid (LNA) anti-miR-221 recently evaluated in NOD.SCID mice. Inhibition of mir-9 with a miRNA sponge make a decrease in the breast cancer metastasis in contrast anti-miR-10b significantly decrease the metastasis but cannot effect in primary tumor growth in breast cancer. Various miRNA antagonists are now under preclinical investigations thus a LNA-anti-mir for Hepatitis C Virus (HCV) called Miravestin is now under phase I and phase IIa clinical trials. RG-101 an anti-miR for mir-122 has undergone to phase I clinical trial. A phase II trial also has performed with RG-101 in combination with real antiviral components like Harvuni that showed a 100% response to drug with no relapse after 24 weeks. These discoveries and clinical trials offer an opportunity for development of miRNA-based cancer-specific therapies. However, it is difficult to identify the best target miRNA for a specific disease.

Keywords:

miR-Antagonist , Cancer , miRNA , AntagomiR