加拿大多伦多大学Housheng Hansen He小组揭示了N⁶-甲基腺苷在局限性原发性前列腺癌中的分布。这一研究成果发表在2025年3月24日出版的国际学术期刊《自然—遗传学》上。

前列腺癌的特点是广泛的转录组失调；因此，课题组人员用匹配的DNA、RNA和蛋白质谱分析了162例局限性前列腺肿瘤的m⁶A结构。m⁶A的丰度在不同的肿瘤中有显著的差异，通过复杂的种-体合作调节形成了全球模式。个体种系多态性调控m⁶A丰度，与肿瘤驱动基因和m⁶A调控因子的体细胞突变协同作用。由此产生的复杂模式与预后临床特征相关，并建立了全球和局部特异性m⁶A模式的生物标志物潜力。肿瘤缺氧失调m⁶A谱，连接先前的基因组和蛋白质组学观察。特定的m⁶A位点，如VCAN中的m⁶A位点，驱动疾病侵袭，与不良预后、肿瘤生长和转移相关。m⁶A基因的失调是否与前列腺癌自然史中的关键事件有关：种系风险、微环境失调、体细胞突变和转移。

据了解，N⁶-甲基腺苷（N⁶-methylladenosine, m⁶A）是人类体内最丰富的内部RNA修饰，调控着RNA加工的大多数方面。

附：英文原文

Title: The landscape of N6-methyladenosine in localized primary prostate cancer

Author: Xu, Xin, Zhu, Helen, Hugh-White, Rupert, Livingstone, Julie, Eng, Stefan, Zeltser, Nicole, Wang, Yujuan, Pajdzik, Kinga, Chen, Sujun, Houlahan, Kathleen E., Luo, Wenqin, Liu, Shun, Xu, Xi, Sheng, Minzhi, Guo, Wang Yuan, Arbet, Jaron, Song, Yuxi, Wang, Miranda, Zeng, Yong, Wang, Shiyan, Zhu, Guanghui, Gao, Tingxiao, Chen, Wei, Ci, Xinpei, Xu, Wenjie, Xu, Kexin, Orain, Michele, Picard, Valerie, Hovington, Helene, Bergeron, Alain, Lacombe, Louis, Ttu, Bernard, Fradet, Yves, Lupien, Mathieu, Wei, Gong-Hong, Koritzinsky, Marianne, Bristow, Robert G., Fleshner, Neil E., Wu, Xue, Shao, Yang, He, Chuan, Berlin, Alejandro, van der Kwast, Theodorus, Leong, Hon, Boutros, Paul C., He, Housheng Hansen

Issue&Volume: 2025-03-24

Abstract: N6-methyladenosine (m6A), the most abundant internal RNA modification in humans, regulates most aspects of RNA processing. Prostate cancer is characterized by widespread transcriptomic dysregulation; therefore, we characterized the m6A landscape of 162 localized prostate tumors with matched DNA, RNA and protein profiling. m6A abundance varied dramatically across tumors, with global patterns emerging via complex germline–somatic cooperative regulation. Individual germline polymorphisms regulated m6A abundance, cooperating with somatic mutation of cancer driver genes and m6A regulators. The resulting complex patterns were associated with prognostic clinical features and established the biomarker potential of global and locus-specific m6A patterns. Tumor hypoxia dysregulates m6A profiles, bridging prior genomic and proteomic observations. Specific m6A sites, such as those in VCAN, drive disease aggression, associating with poor outcomes, tumor growth and metastasis. m6A dysregulation is thus associated with key events in the natural history of prostate cancer: germline risk, microenvironmental dysregulation, somatic mutation and metastasis.

DOI: 10.1038/s41588-025-02128-y

Source: https://www.nature.com/articles/s41588-025-02128-y