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m6A modification confers thermal vulnerability to HPV E7 oncotranscripts via reverse regulation of its reader protein IGF2BP1 upon heat stress.
Wang, Lingfang; Zhan, Guankai; Maimaitiyiming, Yasen; Su, Yingfeng; Lin, Shitong; Liu, Jinfeng; Su, Kunhui; Lin, Jiebo; Shen, Shizhen; He, Wentao; Wang, Fenfen; Chen, Jiafeng; Sun, Siqi; Xue, Yite; Gu, Jiaxin; Chen, Xiaojing; Zhang, Jian; Zhang, Lu; Wang, Qianqian; Chang, Kao-Jung; Chiou, Shih-Hwa; Björklund, Mikael; Naranmandura, Hua; Cheng, Xiaodong; Hsu, Chih-Hung.
Afiliación
  • Wang L; Women's Hospital, Institute of Genetics, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310006, China; Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of M
  • Zhan G; Women's Hospital, Institute of Genetics, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310006, China.
  • Maimaitiyiming Y; Women's Hospital, Institute of Genetics, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310006, China; Department of Hematology of First Affiliated Hospital, and Department of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China; D
  • Su Y; Women's Hospital, Institute of Genetics, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310006, China.
  • Lin S; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • Liu J; Women's Hospital, Institute of Genetics, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310006, China.
  • Su K; Women's Hospital, Institute of Genetics, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310006, China.
  • Lin J; Women's Hospital, Institute of Genetics, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310006, China.
  • Shen S; Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
  • He W; Women's Hospital, Institute of Genetics, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310006, China.
  • Wang F; Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
  • Chen J; Women's Hospital, Institute of Genetics, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310006, China.
  • Sun S; Women's Hospital, Institute of Genetics, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310006, China.
  • Xue Y; Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
  • Gu J; Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
  • Chen X; Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
  • Zhang J; Women's Hospital, Institute of Genetics, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310006, China.
  • Zhang L; Cancer Center, Zhejiang University, Hangzhou 310006, China.
  • Wang Q; Department of Hematology of First Affiliated Hospital, and Department of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China; Cancer Center, Zhejiang University, Hangzhou 310006, China.
  • Chang KJ; Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
  • Chiou SH; Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
  • Björklund M; Zhejiang University-University of Edinburgh (ZJU-UoE) Institute, Haining, Zhejiang 314499, China.
  • Naranmandura H; Department of Hematology of First Affiliated Hospital, and Department of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China; Cancer Center, Zhejiang University, Hangzhou 310006, China. Electronic address: narenman@zju.edu.cn.
  • Cheng X; Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China. Electronic address: chengxd@zju.edu.cn.
  • Hsu CH; Women's Hospital, Institute of Genetics, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310006, China. Electronic address: ch_hsu@zju.edu.cn.
Cell Rep ; 41(4): 111546, 2022 10 25.
Article en En | MEDLINE | ID: mdl-36288717
ABSTRACT
Human papillomavirus (HPV)-induced carcinogenesis critically depends on the viral early protein 7 (E7), making E7 an attractive therapeutic target. Here, we report that the E7 messenger RNA (mRNA)-containing oncotranscript complex can be selectively targeted by heat treatment. In HPV-infected cells, viral E7 mRNA is modified by N6-methyladenosine (m6A) and stabilized by IGF2BP1, a cellular m6A reader. Heat treatment downregulates E7 mRNA and protein by destabilizing IGF2BP1 without the involvement of canonical heat-shock proteins and reverses HPV-associated carcinogenesis in vitro and in vivo. Mechanistically, heat treatment promotes IGF2BP1 aggregation only in the presence of m6A-modified E7 mRNA to form distinct heat-induced m6A E7 mRNA-IGF2BP1 granules, which are resolved by the ubiquitin-proteasome system. Collectively, our results not only show a mutual regulation between m6A RNA and its reader but also provide a heat-treatment-based therapeutic strategy for HPV-associated malignancies by specifically downregulating E7 mRNA-IGF2BP1 oncogenic complex.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Papillomavirus / Alphapapillomavirus Límite: Humans Idioma: En Revista: Cell Rep Año: 2022 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Papillomavirus / Alphapapillomavirus Límite: Humans Idioma: En Revista: Cell Rep Año: 2022 Tipo del documento: Article