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METTL3 modulates m6A modification of CDC25B and promotes head and neck squamous cell carcinoma malignant progression.

Authors
  • Guo, Yu-Qing1
  • Wang, Qiang2
  • Wang, Jun-Guo3, 4
  • Gu, Ya-Jun3, 4
  • Song, Pan-Pan3, 4
  • Wang, Shou-Yu5, 6, 7
  • Qian, Xiao-Yun8, 9, 10, 11
  • Gao, Xia12, 13, 14, 15
  • 1 Medical School of Nanjing University, Nanjing, 210093, Jiangsu, China. , (China)
  • 2 Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China. , (China)
  • 3 Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing, 210008, China. , (China)
  • 4 Research Institute of Otolaryngology, Nanjing, 210008, China. , (China)
  • 5 Medical School of Nanjing University, Nanjing, 210093, Jiangsu, China. [email protected] , (China)
  • 6 Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China. [email protected] , (China)
  • 7 Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, 210093, China. [email protected] , (China)
  • 8 Medical School of Nanjing University, Nanjing, 210093, Jiangsu, China. [email protected] , (China)
  • 9 Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing, 210008, China. [email protected] , (China)
  • 10 Research Institute of Otolaryngology, Nanjing, 210008, China. [email protected] , (China)
  • 11 Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, No.321 Zhongshan Road, Nanjing, 210008, Jiangsu, China. [email protected] , (China)
  • 12 Medical School of Nanjing University, Nanjing, 210093, Jiangsu, China. [email protected] , (China)
  • 13 Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing, 210008, China. [email protected] , (China)
  • 14 Research Institute of Otolaryngology, Nanjing, 210008, China. [email protected] , (China)
  • 15 Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, No.321 Zhongshan Road, Nanjing, 210008, Jiangsu, China. [email protected] , (China)
Type
Published Article
Journal
Experimental Hematology & Oncology
Publisher
Springer Science and Business Media LLC
Publication Date
Mar 14, 2022
Volume
11
Issue
1
Pages
14–14
Identifiers
DOI: 10.1186/s40164-022-00256-3
PMID: 35287752
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

N6-methyladenosine (m6A) RNA methylation and its methyltransferase METTL3 have been widely reported to be involved in different cancers by regulating RNA metabolism and function. Here, we aimed to explore the biological function and clinical significance of m6A modification and METTL3 in head and neck squamous cell carcinoma (HNSCC). The prognostic value of METTL3 expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human HNSCC cohort. The biological role and mechanism of METTL3 in HNSCC tumour growth, metastasis and angiogenesis were determined in vitro and in vivo. M6A levels and METTL3 expressions in HNSCC tissues were significantly increased compared with paired adjacent tissues. Meanwhile, METTL3 was an independent risk factor for the prognosis of HNSCC patients. Moreover, METTL3 overexpression promoted HNSCC cell proliferation, migration, invasion, and angiogenesis, while knockdown of METTL3 had an opposite effect in vivo and in vitro. Mechanistically, METTL3 enhanced the m6A modification of CDC25B mRNA, which maintained its stability and upregulated its expression, thereby activating G2/M phase of cell cycle and leading to HNSCC malignant progression. METTL3 may be a potential prognostic biomarker and therapeutic target for HNSCC. © 2022. The Author(s).

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