MicroRNAs (miRNAs) are non-coding RNAs, which are used generally to down-regulate gene expression from messenger RNA (mRNA) by binding to it. miRNAs are getting popular in potential application in cancer therapy. They could be used either to replace tumour suppressive miRNA lost in cancer or to inhibit oncogenic miRNA, which is overexpressed in cancer.
miRNAs are small single-stranded RNAs, usually consistent of 18-26 nucleotides. Mature miRNAs have RNA-induced silencing complex (RISC), which allows them to target many mRNAs. They use this mechanism to down-regulate mRNA. According to some predictions – each miRNA could regulate up to 200 individual mRNAs.
In cancer tumours use different mechanisms to overcome the control of the normal cells. The role of miRNAs was first studied in 2002 in chronic lymphocytic leukaemia. There are several well-studied miRNAs that have oncogenic or tumour suppressive functions. Currently there are over 2 500 known miRNA but the functions of many of them as still unknown.
However there are some limitations in miRNA application:
There should be very careful selection of the target as one miRNA could interact with many mRNAs and affect different processes.
Current miRNA process involves targeting or imitating specific miRNA, which is involved in cancer related process. Therapeutic targeting may need miRNA to act as an oncogene or as a tumour suppressor.
Approaches that could be used in oncology
Loss of cell-cell adhesion allow cancer cells to enter blood-stream and reach distant sites. There are miRNAs that target epithelia-to-mesenchymal transition, which is critical regulator of metastasis. There are artificial miRNAs that have shown to inhibit transformation, migration and invasiveness in vitro and suppress tumourigenicity in vivo.
Targeting cancer cells and blocking their activity is a well-known strategy. There are many miRNAs involved in the process and currently over 40 miRNAs were identified. Many are involved in cell cycle suppression.
miRNAs could be used to overcome chemotherapy resistance. There are evidence that chemotherapy resistance is result of epigenetic modifications and they are controlled by miRNAs. There is research to use miRNAs for delivery agents in combination of DNA damaging agents or chemotherapy.
miRNAs are shown to be involved in tumour immune response and this makes them attractive potential therapeutic agent that can modulate immune response and suppress tumour metastasis.
While miRNA provide exciting new opportunities in oncology, there are still many unknown potential interactions and side effects which need to be studied. RNA technologies are definitely an exciting field to follow in the future.
Published on 4 January 2018
Author: Olga Peycheva, Director at Solutions OP Ltd. Olga has been working in clinical research since 2005 and has extensive experience in Eastern and Western Europe
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