ALKBH5 promotes hypopharyngeal squamous cell carcinoma apoptosis by targeting TLR2 in a YTHDF1/IGF2BP2-mediated manner

Jing Ye; Yuting Wu; Yao Chen; Yiyue Ren; Xiaohua Jiang; Zhihuai Dong; Jingna Zhang; Mao Jin; Xiaozhen Chen; Zhanggui Wang; Mang Xiao

doi:10.1038/s41420-023-01589-6

Cell Death Discovery (Aug 2023)

ALKBH5 promotes hypopharyngeal squamous cell carcinoma apoptosis by targeting TLR2 in a YTHDF1/IGF2BP2-mediated manner

Jing Ye,
Yuting Wu,
Yao Chen,
Yiyue Ren,
Xiaohua Jiang,
Zhihuai Dong,
Jingna Zhang,
Mao Jin,
Xiaozhen Chen,
Zhanggui Wang,
Mang Xiao

Affiliations

Jing Ye: Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang `University
Yuting Wu: Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang `University
Yao Chen: Department of Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University
Yiyue Ren: Department of Head and Neck Surgery, Institute of Micro-Invasive Surgery of Zhejiang University, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University Hangzhou
Xiaohua Jiang: Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang `University
Zhihuai Dong: Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang `University
Jingna Zhang: Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang `University
Mao Jin: Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang `University
Xiaozhen Chen: Central Laboratory, Institute of Clinical Science, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University Hangzhou
Zhanggui Wang: Department of Radiotherapy, The Second People’s Hospital of Anhui Province
Mang Xiao: Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang `University

DOI: https://doi.org/10.1038/s41420-023-01589-6
Journal volume & issue: Vol. 9, no. 1
pp. 1 – 14

Abstract

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Abstract Hypopharyngeal squamous cell carcinoma (HPSCC) is one of the most aggressive cancers and is notorious for its extremely poor prognosis. However, very few molecular biological studies have been performed. As a novel method of epigenetic gene modulation, N6-methyladenosine (m6A) RNA modification occurs in HPSCC. The expression of the m6A demethylase AlkB homolog 5 (ALKBH5) is frequently downregulated in human HPSCC. Furthermore, we found that ALKBH5 impaired cell proliferation by regulating human Toll-like receptor 2 (TLR2) in an m6A-dependent manner in HPSCC cells. ALKBH5 decreased TLR2 m6A modification, which could be recognized by the m6A readers IGF2BP2 and YTHDF1. IGF2BP2 facilitates TLR2 mRNA stability, whereas YTHDF1 promotes TLR2 mRNA translation. The current work uncovered a critical function of ALKBH5 in TLR2 regulation and provides a novel role for m6A demethylation of mRNA in HPSCC. The inhibition of m6A modification of ALKBH5 in HPSCC deserves further clinical investigation.

Published in Cell Death Discovery

ISSN: 2058-7716 (Online)
Publisher: Nature Publishing Group
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Science: Biology (General): Cytology
Website: http://www.nature.com/cddiscovery/

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