The landscape of N6-methyladenosine in localized primary prostate cancer

被引：0

作者：

Xin Xu ^{[1
]}

Helen Zhu ^{[1
]}

Rupert Hugh-White ^{[2
]}

Julie Livingstone ^{[3
]}

Stefan Eng ^{[4
]}

Nicole Zeltser ^{[5
]}

Yujuan Wang ^{[6
]}

Kinga Pajdzik ^{[7
]}

Sujun Chen ^{[4
]}

Kathleen E. Houlahan ^{[5
]}

Wenqin Luo ^{[6
]}

Shun Liu ^{[7
]}

Xi Xu ^{[4
]}

Minzhi Sheng ^{[5
]}

Wang Yuan Guo ^{[6
]}

Jaron Arbet ^{[7
]}

Yuxi Song ^{[4
]}

Miranda Wang ^{[5
]}

Yong Zeng ^{[6
]}

Shiyan Wang ^{[7
]}

Guanghui Zhu ^{[1
]}

Tingxiao Gao ^{[8
]}

Wei Chen ^{[9
]}

Xinpei Ci ^{[1
]}

Wenjie Xu ^{[2
]}

Kexin Xu ^{[21
]}

Michele Orain ^{[2
]}

Valerie Picard ^{[3
]}

Helene Hovington ^{[4
]}

Alain Bergeron ^{[5
]}

Louis Lacombe ^{[6
]}

Bernard Têtu ^{[7
]}

Yves Fradet ^{[1
]}

Mathieu Lupien ^{[10
]}

Gong-Hong Wei ^{[8
]}

Marianne Koritzinsky ^{[9
]}

Robert G. Bristow ^{[1
]}

Neil E. Fleshner ^{[2
]}

Xue Wu ^{[11
]}

Yang Shao ^{[1
]}

Chuan He ^{[4
]}

Alejandro Berlin ^{[5
]}

Theodorus van der Kwast ^{[6
]}

Hon Leong ^{[7
]}

Paul C. Boutros ^{[4
]}

Housheng Hansen He ^{[5
]}

机构：

[1] University Health Network,Princess Margaret Cancer Center

[2] University of Toronto,Department of Medical Biophysics

[3] Vector Institute,Department of Urology

[4] University of California,Institute for Precision Health

[5] Los Angeles,Jonsson Comprehensive Cancer Centre

[6] University of California,Department of Human Genetics

[7] Los Angeles,Department of Chemistry

[8] University of California,Howard Hughes Medical Institute

[9] Los Angeles,Department of Urology, Sir Run Run Shaw Hospital

[10] University of California,MOE Key Laboratory of Metabolism and Molecular Medicine and Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Fudan University Shanghai Cancer Center

[11] Los Angeles,Department of Molecular Medicine

[12] the University of Chicago,State Key Laboratory of Common Mechanism Research for Major Disease, Suzhou Institute of Systems Medicine

[13] the University of Chicago,Division of Cancer Sciences

[14] Zhejiang University School of Medicine,Geneseeq Research Institute

[15] Sunnybrook Research Institute,School of Public Health

[16] Shanghai Medical College of Fudan University,Department of Pharmacology and Toxicology

[17] University of Texas Health Science Center at San Antonio,West China School of Public Health, West China Fourth Hospital and State Key Laboratory of Biotherapy

[18] Research Centre of CHU de Québec-Université Laval,Institute of Precision Medicine, First Affiliated Hospital

[19] Chinese Academy of Medical Sciences and Peking Union Medical College,Department of Respiratory and Critical Care Medicine

[20] University of Manchester,undefined

[21] Christie NHS Trust and CRUK Manchester Institute and Cancer Centre,undefined

[22] Geneseeq Technology lnc.,undefined

[23] Nanjing Medical University,undefined

[24] University of Toronto,undefined

[25] Sichuan University,undefined

[26] Sun Yat-sen University,undefined

[27] the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University,undefined

来源：

Nature Genetics | 2025年 / 57卷 / 4期

关键词：

D O I：

10.1038/s41588-025-02128-y

中图分类号：

学科分类号：

摘要：

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.

引用

页码：934 / 948

页数：14

共 50 条

[1] Systematic Investigation of mRNA N6-Methyladenosine Machinery in Primary Prostate Cancer
Jiang, Mei
Lu, Yali
Duan, Dongxia
Wang, Hongxiang
Man, Gaoya
Kang, Ching
Abulimiti, Kesaier
Li, Yao
DISEASE MARKERS, 2020, 2020
[2] Functions and mechanisms of N6-methyladenosine in prostate cancer
Wan, Hongyuan
Feng, Yanyan
Wu, Junjie
Zhu, Lijie
Mi, Yuanyuan
MOLECULAR MEDICINE REPORTS, 2022, 26 (03)
[3] Modulation of translation regulation by N6-methyladenosine in prostate cancer.
Cotter, Kellie A.
Meyer, Kate D.
Benelli, Matteo
Cohen, Sandra
Jaffrey, Samie
Demichelis, Francesca
Rubin, Mark
CANCER RESEARCH, 2018, 78 (16) : 47 - 47
[4] The N6-methyladenosine Epitranscriptomic Landscape of Lung Adenocarcinoma
Wang, Shiyan
Zeng, Yong
Zhu, Lin
Zhang, Min
Zhou, Lei
Yang, Weixiong
Luo, Weishan
Wang, Lina
Liu, Yanming
Zhu, Helen
Xu, Xin
Su, Peiran
Zhang, Xinyue
Ahmed, Musaddeque
Chen, Wei
Chen, Moliang
Chen, Sujun
Slobodyanyuk, Mykhaylo
Xie, Zhongpeng
Guan, Jiansheng
Zhang, Wen
Khan, Aafaque Ahmad
Sakashita, Shingo
Liu, Ni
Pham, Nhu-An
Boutros, Paul C.
Ke, Zunfu
Moran, Michael F.
Cai, Zongwei
Cheng, Chao
Yu, Jun
Tsao, Ming S.
He, Housheng H.
CANCER DISCOVERY, 2024, 14 (11) : 2279 - 2299
[5] Emerging function of N6-methyladenosine in cancer
Hong, Kwonho
ONCOLOGY LETTERS, 2018, 16 (05) : 5519 - 5524
[6] N6-methyladenosine RNA methylation regulators contribute to the progression of prostate cancer
Wu, Qunying
Xie, Xing
Huang, Yiming
Meng, Shanshan
Li, Youcheng
Wang, Huifeng
Hu, Yanling
JOURNAL OF CANCER, 2021, 12 (03): : 682 - 692
[7] Role of N6-methyladenosine in the pathogenesis, diagnosis and treatment of prostate cancer (Review)
Pan, Junjie
Tong, Fei
Ren, Ning
Ren, Lanqi
Yang, Yibei
Gao, Feng
Xu, Qiaoping
ONCOLOGY REPORTS, 2024, 51 (06)
[8] Refining the role of N6-methyladenosine in cancer
Koch, Jonas
Lyko, Frank
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2024, 88
[9] Role of N6-methyladenosine modification in cancer
Deng, Xiaolan
Su, Rui
Feng, Xuesong
Wei, Minjie
Chen, Jianjun
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2018, 48 : 1 - 7
[10] The N6-methyladenosine RNA landscape in the aged mouse hippocampus
Huang, He
Song, Renhua
Wong, Justin J. -L.
Anggono, Victor
Widagdo, Jocelyn
AGING CELL, 2023, 22 (01)

← 1 2 3 4 5 →