It is very common that microRNAs are overexpressed or inactivated in human diseases. The best approach in such cases is to either target the overexpressed microRNA to inactivate it or replace the inactive microRNA.

But let’s first review what is microRNA and what is their role.

MicroRNAs are small noncoding RNAs that are approximately 20-25 nucleotides in length. Most microRNAs are the same in different animal species, which underline the importance of microRNA in the evolution. The process of inactivating the microRNAs does not require perfect complimentary recognition of the target, because only the 6 to 8 nucleotides in the 5’ portion of microRNAs is sufficient to trigger interaction. Also single microRNA can regulate multiple mRNAs. More importantly the ability of microRNAs to influence entire network of gene involve in common cellular process provide great therapeutic opportunity. 

miR-122 and hepatitis C

miR-122 is a microRNA expressed in liver, which helps hepatitis C virus (HCV) to replicate once it reaches the liver. It’s natural role in the liver is to regulate its metabolic functions – cholesterol homeostasis, fatty acids and lipid metabolism. miR-122 is conservative to HCV across all genotypes and subtypes. A clinical study using SPC3649, 15 nucleotide phosphorothioate oligonucleotide, has shown positive results in monkeys.

miR-33 and atherosclerosis

One of the potential mechanisms of eliminating LDL cholesterol involves efflux from the macrophages in atherosclerotic vascular lesions to circulating HDL, which will help to be excreted into the faeces. Studies have shown that miR-33a/b inhibit the expression of the cholesterol transporter ABCA1, which result of increased levels of atheroprotective plasma HDL. Mice models have shown that inhibition of miR-33 raise plasma HDL and support lowering of LDL. 

miR-221 in hepatocellular carcinoma

miR-221/222 cluster has been reported to be over-expressed in multiple cancers, including hepatocellular carcinoma. miR-221 is reported to be expressed at a higher level than miR-222. The reason for the over-expression is unknown, however it was shown in human studies that the level of serum miR-221 in patients with hepatocellular carcinoma correlate with tumour size, stage and patient survival. This makes miR-221 important target in cancer research. 

MicroRNAs definitely provide unique opportunity in drug development. Different studies show that microRNA inhibitors can have effect on different diseases. 

Source: Therapeutic modulation of microRNAs

Author: Olga Peycheva

Olga is a clinical research professional who has been working in clinical research since 2005. She has extensive experience in clinical research in Eastern and Western Europe. 

Originally published on 2 Sep 2019