Researchers at VTT Technical Research Centre of Finland, the University of
Turku and the University of Oslo have discovered a previously unknown
molecular-level mechanism that may partly explain the increased growth of
cancer cells. The study, published in the British Journal of Cancer, showed
that high levels of miRNA-378a-5p molecule cause cell division anomalies. This
renders the number of chromosomes in cancer cells abnormal, which is known to
promote growth and the spread of cancer. In addition, the researchers
discovered that elevated miRNA378a-5p levels in breast cancer patients
correlate with the most aggressive forms of cancer. The objective is to
develop new diagnostic methods for breast cancer on the basis of the research
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.