microRNA Activity Insights Could be Key to New Cancer Treatments

One of the major scientific crusades in oncology has been to identify and validate biomarkers associated with recurrent breast cancer. [iStock / royaltystockphoto]

New research out of Sweden shows that microRNAs associated with cancer risk can alter their structure and change the amount of protein produced in a cell, which the scientists believe could lead to the development of new types of cancer therapies.

Micro (mi)RNAs are normally between 19 and 25 nucleotides in length and play a role in regulating the expression of genes. A single miRNA can regulate a number of genes through its impact on messenger (m)RNA, which acts to translate the genes encoded in our DNA into proteins in our cells.

While miRNAs can regulate many genes, they have been shown to have a strong impact on cancer development and on processes such as cancer drug resistance. The exact way they do this is not totally clear, but it is known that miRNAs have the ability to ‘silence’ mRNA and, in so doing, prevent protein production.

“It’s important to increase our understanding of how miRNA regulates protein production because this process is disturbed in many different types of diseases, including cancer,” commented Katja Petzold, PhD, from the Karolinska Institutet in Sweden, who led the study.

The research, which was published in Nature, looked at a miRNA called miR-34a, which plays a known role in cancer by influencing expression of the well-known tumor suppressing protein p53. It does this indirectly by reducing the amount of mRNA that codes for a protein called Sirt1 that in turn is able to deactivate p53.

Petzold and team used nuclear magnetic resonance imaging and other methods to decipher how miR-34a is able to change the amount of protein made in a cell. They found that it can change its form into two different structures – a rare form (around 1%) with high activity and a much more common form (around 99%) with only moderate activity. The different forms influence how much of the protein encoded by miR-34a’s partner mRNA is made in the cell. They also observed that these two forms seem to be interchangeable and the proportions in a cell can change depending on unknown external factors.

“We show for the first time that a miRNA-mRNA complex has a structure that changes and that this movement has an effect on the biological outcome,” said Petzold.

This ‘switch’ can be flipped by the rearrangement of a single base pair binding between the miRNA and its partner mRNA. “Once we find out how to turn the switch, we can use this in the clinic as a drug to control the production of specific proteins,” emphasized Petzold.

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