A collaboration between the Garvan Institute of Medical Research and Peter Mac has shed light on how cancer cells can precisely control their behaviour through the action of tiny micro-RNAs. They found these small molecules can make a very big impact on whether a cancer cell lives or dies.

Published in the journal Nucleic Acids Research, the study led by Dr Iva Nikolic at Peter Mac and A/Prof Alex Swarbrick at the Garvan has identified which micro-RNAs (miRNAs) are important in determining whether a cancer cell survives.

miRNAs are small strands of genetic material that have the power to control what signals get turned on and off inside a cell. Through this activity miRNAs can control how a cancer cell behaves, from how they divide to how they spread through the body, and even how they respond to treatments.

There are thousands of different miRNAs in every cell, but until now it has been difficult to assess which of these are important in cancer.

 “Most other studies into miRNAs in cancer have looked simply at how many miRNA molecules are in a cell, but not at what they are doing,” says the study’s lead author, Dr Iva Nikolic, senior postdoctoral research fellow at the Victorian Centre for Functional Genomics (VCFG) at Peter Mac.

Dr Nikolic, who was at the time a visiting scientist at Peter Mac from A/Prof Alex Swarbrick’s laboratory at the Garvan, conducted her research largely within the VCFG using high-throughput technologies headed by A/Prof Kaylene Simpson.

“In our study we used techniques that allowed us to either mimic or stop the action of individual miRNAs inside cancer cells and looked to see whether the cells survived or died,” explains Dr Nikolic.

miRNAs are powerful molecules inside a cell with the ability to regulate the expression of not just one, but many different downstream genes.

“By targeting single miRNAs we were able to study the function of whole gene networks and determine their importance in cancer cell function.”

Another unique feature of the study was its assessment of many different cell lines representing diverse cancer types, allowing scientists to draw closer connections between gene expression and cell behaviours that has not been possible in smaller studies.

 “We studied the action of each miRNA in the contexts of different cancer types and found quite big differences. For example, miRNAs in breast cancer cells act in different ways to miRNAs in prostate or brain cancer cells.”

“Therefore, miRNA-dependent regulation of cancer is likely determined by the cell type from which the cancer was originally derived. This will help us think about better treatments tailored for cancer type,” says Dr Nikolic.

The study authors also developed a web-based portal that will help cancer researchers from all over the world predict direct targets of individual miRNAs within cancer cells. This may aid the identification of new targets for anti-cancer therapies.

“It was an important aim of the study to create a resource for other scientists to be able to learn from our research. We hope this will help to find new insights into how cancers work and drive new discoveries.”