Skin cancer suppressor found
Although the research is at an early stage, the team hope that their work could help develop new ways to combat melanoma and potentially other cancers too.
The team from the University of Bath’s Department of Biology & Biochemistry were researching a group of ‘long non-coding RNAs’ (IncRNAs) with colleagues at the Ludwig Institute for Cancer Research at the University of Oxford, the Wellcome Sanger Institute and University of Lausanne, Switzerland.
IncRNAs are molecules transcribed from our DNA that don’t make protein and whose functions remain largely unknown. The particular group of IncRNAs the team were interested in are thought to be involved in cancer.
From a group of 245 IncRNAs that were associated with melanomas they identified one, called _Disrupted In Renal Carcinoma 3 (DIRC3)_, which acted as a tumour suppressor to block the spread of human melanoma cells when grown in lab experiments.
By using gene-editing to switch off production of _DIRC3_, the team saw that “anchorage-independent growth” — a hallmark of malignant cancer spread — drastically increased by between two to eight times.
Furthermore the scientists showed that _DIRC3_ switches on the key tumour suppressor IGFBP5 gene, revealing that it plays a role in the complex networks governing the expression of genes important for melanoma growth and spread to other parts of the body.
The researchers used The Cancer Genome Atlas clinical data to link _DIRC3_ expression to melanoma patient outcomes. They discovered that melanoma patients who produced high levels of _DIRC3_ had statistically significant increased survival rates compared to patients who expressed low levels.
The study is published in PLOS Genetics.
Dr Keith Vance, from the University of Bath Department of Biology & Biochemistry, said: “Although it’s early stages we are excited by the potential of _DIRC3_ activating drugs to become a new way to treat skin cancer. This research makes vital steps towards any future therapy development.
“Great strides have recently been made in treating melanoma. However, not all patients respond to current therapies and most skin cancers become drug resistant over time, so a new way to treat it could be another tool in combatting the disease.
“By investigating how _DIRC3_ works we can really start to understand how it blocks the spread of melanoma in detail at the molecular level, and identify druggable interfaces and specific structures that could be targets for medicine.”
The study was funded by the Biological and Biotechnology Research Council (BBSRC), the Skin Cancer Research Fund, and The Royal Society.