Clinical applications of microRNAs

Per Hydbring,Gayane Badalian-Very

doi:10.12688/f1000research.2-136.v1

Per Hydbring, Gayane Badalian-Very

Open Access

https://doi.org/10.12688/f1000research.2-136.v1

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Abstract

MicroRNAs represent a class of small RNAs derived from polymerase II controlled transcriptional regions. The primary transcript forms one or several bulging double stranded hairpins which are processed by Drosha and Dicer into hetero-duplexes. The targeting microRNA strand of the duplex is incorporated into the RNA Induced Silencing Complex from where it silences up to hundreds of mRNA transcript by inducing mRNA degradation or blocking protein translation. Apart from involvement in a variety of biological processes, microRNAs were early recognized for their potential in disease diagnostics and therapeutics. Due to their stability, microRNAs could be used as biomarkers. Currently, there are microRNA panels helping physicians determining the origins of cancer in disseminated tumors. The development of microRNA therapeutics has proved more challenging mainly due to delivery issues. However, one drug is already in clinical trials and several more await entering clinical phases. This review summarizes what has been recognized pre-clinically and clinically on diagnostic microRNAs. In addition, it highlights individual microRNA drugs in running platforms driven by four leading microRNA-therapeutic companies.

Highlights

MicroRNAs represent a class of small RNAs derived from polymerase II controlled transcriptional regions
MicroRNA discovery Two decades have passed since the groundbreaking work from the laboratories of Gary Ruvkun and Victor Ambros, which demonstrated that a small temporal non-coding RNA could influence development of Caenorhabditis elegans by base pairing to the 3′ untranslated region (3′UTR) of a coding messenger RNA thereby regulating its translation[1,2]
These findings suggest that most miRNAs are transcriptionally regulated in a “protein-coding like” fashion

Summary

Reviewer Status

Any reports and responses or comments on the article can be found at the end of the article. Prostate cancer patients could be distinguished from healthy counterparts by analyzing the expression level of miR-14330 These studies were followed by additional reports of miRNAs in breast cancer (using whole blood)[42], colorectal cancer (using plasma)[43] and squamous cell lung cancer (using sputum)[44] patients. MicroRNA profiling methods miRNA expression profiling and disease association studies are conducted using a set of different methods including miRNA microarray platforms, quantitative real-time polymerase chain reaction (qRT-PCR), in situ hybridization and high throughput sequencing. Both qRT-PCR and hybridization methods are highly sensitive and quantitative.

Node MicroRNAs used at node

Findings

SANTARIS PHARMA