Epigenetics discovery aids prostate cancer diagnosis

A lot of attention has been placed on the genetics of cancer, including looking at the mutations that occur that enable a small cohort of cells to maintain runaway growth.

But cancer also sees changes occur at the epigenetic level, switching key genes on and off to enable it to grow and spread.

Now researchers at Sydney’s Garvan Institute have revealed the role of one non-coding microRNA (miRNA) which appears to play a significant role in prostate cancer and is closely linked to the prognosis of cancer patients.

The discovery opens up the possibility of developing a new diagnostic tool as well as yielding an insight into how prostate cancer proliferates, and how it might potentially be stopped.

The miRNA in question is miR-205, and the team found it was downregulated in prostate cancer cells, particularly in aggressive and metastatic examples.

miR-205, in turn, regulates a gene MED1, which influences cell proliferation in prostate cells, keeping it in check so that proliferation doesn’t run out of control. As such, overexpression of miR-205 has an impact on cell viability, acting as a tumour suppressor.

However, the team, led by Dr Toby Hulf and Professor Susan Clark, found that prostate cancer cells has lower levels of miR-205, thus enabling MED1 to encourage cell proliferation and the development of a tumour.

They also worked with two other Garvan researchers, Professor Rob Sutherland and Clinical Associate Professor Lisa Horvath, to look at patients with prostate cancer, separating them into groups with good and poor prognosis.

They found that those with poor prognosis appeared to have greater methylation of miR-205, suggesting that levels of the miRNA could be used as a diagnosis tool to determine likely progression and prognosis of prostate cancer.

“We are excited, because this is the first study to investigate this class of microRNAs at the epigenetic level in prostate cancer,” said Professor Susan Clark.

“The epigenome is a constantly changing set of biochemical modifications that directly impact upon gene expression – and in this case we showed extensive methylation of at least 10 microRNAs involved in prostate cancer, especially miRNA-205.”

“Methylation has the effect of silencing a gene, and in this study hypermethylation of miRNA-205 was directly associated with poor prognosis for prostate cancer patients.”

“This is a novel finding and we now aim to use this potential translational biomarker to screen a much larger clinical cohort, investigating how it might be used in the management of prostate cancer.”

The study was published in the journal Oncogene today.