FINDINGS
Scientists at the UCLA Health Jonsson Comprehensive Cancer Center and the University of Toronto have revealed how a tiny chemical modification in RNA, known as m6A, plays a critical role in the progression of prostate cancer, including driving some of its most dangerous forms of the disease.
In the most comprehensive analysis yet of m6A in prostate cancer, researchers mapped these modifications across 162 prostate cancer tumors and found that m6A patterns were closely tied to how aggressive a tumor was. In some cases, they acted like a molecular fingerprint, marking cancers that were more likely to grow quickly and spread. In others, the m6A tags appeared to be active players, helping cancer cells multiply, migrate and invade new tissue.
One of the key discoveries involved a gene called VCAN, which produces a protein linked to tumor growth. When m6A tags were added to VCAN’s RNA, the cancer became more aggressive and more likely to metastasize. Targeting these modifications could offer a new way to slow down or stop the disease.
The researchers also found m6A modifications can act as biomarkers to predict disease behavior, suggesting that analyzing m6A tags could help doctors determine how a patient’s prostate cancer will behave and whether it’s likely to be slow-growing or aggressive.
BACKGROUND
Prostate cancer remains one of the leading causes of cancer-related deaths among men, with treatment outcomes varying widely. While much focus has been placed on genetic mutations in the DNA, recent research has pointed to the importance of post-transcriptional modifications, which are chemical changes made to RNA molecules, as critical regulators of cancer behavior. One of the most abundant and significant modifications in RNA is m6A, which influences RNA processing, stability, and translation into proteins. However, its role in cancer—particularly prostate cancer—has not been fully understood.
IMPACT
By focusing on m6A modifications, the study paves the way for more accurate predictions of cancer aggressiveness and more personalized treatment strategies. The findings suggest that m6A patterns could serve as biomarkers to help doctors determine how likely a prostate cancer tumor is to grow or spread. They also highlight potential new therapies that target m6A modifications, particularly on genes like VCAN, to prevent cancer progression and metastasis.
JOURNAL
The study was published in Nature Genetics .
AUTHORS
The study’s first co-authors are Rupert Hugh-White and Julie Livingstone from UCLA, and Xin Xu and Helen Zhu from the University of Toronto. The senior co-authors are Dr. Paul Boutros , professor of urology and human genetics and interim vice dean for the David Geffen School of Medicine at UCLA and director of cancer data science at the UCLA Health Jonsson Comprehensive Cancer Center, and Dr. Housheng Hansen He, professor of medical biophysics at the University of Toronto.
FUNDING
The study was funded in part by the Princess Margaret Cancer Foundation, the Canadian Cancer Society, CIHR operating grants, the Terry Fox New Frontiers Program Project Grant, the National Institutes of Health and Prostate Cancer Foundation. A full list of funders is available on the paper.
Nature Genetics