MicroRNAs are small intracellular RNA molecules that regulate gene expression. Therefore, they play important roles in various normal processes of the human body, such as embryogenesis, and the regulation of cell viability. In addition, it is known that abnormal amounts of microRNA stimulate the onset and development of different diseases, such as cancer.
The objective of the research project lead by Marko Kallio, Principal Scientist at VTT, was to identify novel microRNAs participating in the regulation of cell division among the over 1000 microRNAs found in human. In the study it was found that elevated miR-378a-5p levels perturb mitotic fidelity, which is known to be one of the factors promoting the generation, growth and spread of cancer.
The researchers also succeeded in discovering a molecule-level mechanism that can explain the observed chromosome changes caused by over-expression of miR-378a-5p; excess of this particular microRNA in cancer cells leads to significant suppression of Aurora B kinase, which is an essential protein needed for faithful cell division. In addition, over-expression of miR-378a-5p was found to reduce the sensitivity of cancer cells to paclitaxel treatment and to activate certain cell surface receptors, which transmit signals regulating, for example, angiogenesis. The observation concerning activation of receptors is consistent with a Canadian study published earlier showing that over-expression of miR-378a-5p stimulates neovascularization in tumours.
In addition to the new observations concerning pathogenesis of cancer and drug response of cancer cells, the Finnish-Norwegian study is also significant due to the research results obtained from the tumours of breast cancer patients. Elevated miR-378a-5p levels were detected particularly in the most aggressive grade 3 breast tumours, which have poor patient outlook. In the future, the research group will attempt to verify the results in a more extensive patient study, with the additional objective of developing new diagnostic methods based on the expression of microRNA molecules.
The results of the research project headed by Dr. Kallio give new perspectives on earlier microRNA studies, and reinforce the theory that cancer cells take advantage of microRNA molecules when striving to multiply and spread. In case of the miR-378a-5p, its over-expression in cancer tissue may stimulate angiogenesis in tumours, enhance the energy metabolism of cancer cells, reduce the sensitivity of cancer cells to paclitaxel therapy, and induce chromosome changes, that all help cancer gain growth advantage.