Cancer Research in the Loop

Findings published in Cell have revealed that a rarely studied type of genetic material—known as circular RNA—is prevalent in prostate cancer and some of this genetic material is essential for growth of the cancer.

The work was carried out in the labs of Drs. Housheng Hansen He at the Princess Margaret Cancer Centre and Paul Boutros at the University of California, Los Angeles (formerly at the Ontario Institute of Cancer Research).

“Novel sequencing approaches have opened up a new realm of research. By studying this circular genetic material in prostate cancer, we’ve uncovered a wealth of insight into how the cancer grows and spreads, while uncovering potential new strategies to target and kill it.” says Dr. He, lead author of the study.

The main type of genetic material in the cell—known as genomic DNA—serves as the ‘source book’ that holds the information required by cells to carry out chemical reactions required for life. DNA is also used by the cell to create or ‘code for’ other forms of genetic material, including RNA, which is thought of as the ‘working copy’ of the genetic code.

Much of the DNA and RNA found in the cell resembles a string or rope of varying lengths; however, some of it can be joined end to end to create a circular molecule.

Dr. He and his collaborators began to suspect that circular RNA may be important for prostate cancer growth because previous studies have suggested that various distinct forms of RNA are present in prostate cancer cells. As well, circular RNA has been implicated in other types of cancers, such as colon and breast cancer.

The researchers used a technique known as ultra-deep sequencing to define the circular RNA present within 144 tumours from patients with prostate cancer. They identified over 76,000 circular RNAs—more than 30,000 of which had not been previously described.

The researchers then compared the genetic data to patient outcomes, revealing that tumours from individuals with the most aggressive types of prostate cancer tended to have aberrant production of circular RNAs.

The researchers took this work one step further by targeting and inhibiting specific circular RNA molecules in experimental models of prostate cancer. They found that around 11% of the circular RNA was important for driving cancer growth—emphasizing its potential to serve as a new anticancer target.

This work was supported by the Princess Margaret Cancer Foundation, the Princess Margaret Genomic Centre, the Ontario Institute for Cancer Research, Prostate Cancer Canada, Terry Fox Research Institute, the Canada Foundation for Innovation, the Ontario Research Fund, the Natural Sciences and Engineering Research Council of Canada, the Canadian Cancer Society, the Canadian Institutes of Health Research, the Shanghai Committee of Science and Technology, University of Toronto and The Center for Translational Molecular Medicine.

Chen S, et al. Widespread and Functional RNA Circularization in Localized Prostate Cancer. Cell. 2019 Feb 7. doi: https://doi.org/10.1016/j.cell.2019.01.025.