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Article Abstract
Introduction: N1-methyladenosine (m1A) RNA methylation is an emerging epigenetic modification. Its potential role in lipid metabolism and prognosis of prostate cancer (PCa) remains unexplored.
Objectives: This study investigated the impact of m1A on lipid metabolism and PCa prognosis.
Methods: In this work, the landscape of genetic and expression variations of 10 widely recognized m1A regulators in PCa was revealed. Combining machine-learning strategies, the m1A modification patterns and corresponding characteristics of lipid metabolism of PCa samples from the cancer genome atlas program (TCGA) dataset were comprehensively analyzed. In vitro assays were performed to identify the role of TRMT61A, the key m1A regulator, on PCa cells.
Results: Two distinct m1A modification patterns and corresponding lipid metabolism profiles were identified in PCa. The m1A modification subgroup with a high risk of biochemical recurrence (BCR) has stronger mitochondrial metabolism and FA oxidation activity. A consensus m1A modification-related lipid metabolism score (mMLMS) was constructed to predict the BCR prognosis of patients with PCa. The mMLMS was shown to accurately predict the BCR prognosis of PCa within six external cohorts. Finally, TRMT61A was identified as the key m1A regulator related to mMLMS, and it was found to promote the progression of PCa in vitro. TRMT61A potentially enhances mitochondrial function and FA beta oxidation in PCa cells via the PI3K/AKT pathway.
Conclusion: m1A RNA methylation patterns are associated with characteristics of lipid metabolism in PCa, providing a novel treatment strategy.
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| http://dx.doi.org/10.1016/j.intimp.2024.113404 | DOI Listing |
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