PMID- 38048860 OWN - NLM STAT- MEDLINE DCOM- 20240101 LR - 20240322 IS - 1873-3913 (Electronic) IS - 0898-6568 (Linking) VI - 114 DP - 2024 Feb TI - M6A reader YTHDF1 promotes malignant progression of laryngeal squamous carcinoma through activating the EMT pathway by EIF4A3. PG - 111002 LID - S0898-6568(23)00417-5 [pii] LID - 10.1016/j.cellsig.2023.111002 [doi] AB - Laryngeal squamous cell carcinoma (LSCC) is one of the common malignant tumors in the head and neck region, and its high migration and invasion seriously threaten the survival and health of patients. In cancer development, m6A RNA modification plays a crucial role in regulating gene expression and signaling. This study delved into the function and mechanism of the m6A reading protein YTHDF1 in LSCC. It was found that YTHDF1 was highly expressed in the GEO database and LSCC tissues. Cell function experiments confirmed that the downregulation of YTHDF1 significantly inhibited the proliferation, migration, and invasion ability of LSCC cells. Further studies revealed that EIF4A3 was a downstream target gene of YTHDF1, and knockdown of EIF4A3 similarly significantly inhibited the malignant progression of LSCC in both in vivo and in vitro experiments. The molecular mechanism studies suggested that YTHDF1-EIF4A3 may promote the malignant development of LSCC by activating the EMT signaling pathway. This study provides important clues for an in-depth understanding of the pathogenesis of LSCC and is a solid foundation for the discovery of new therapeutic targets and approaches. CI - Copyright (c) 2023. Published by Elsevier Inc. FAU - Guo, Huina AU - Guo H AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China. FAU - Han, Qi AU - Han Q AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China. FAU - Guan, Xiaoya AU - Guan X AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China. FAU - Li, Zhongxun AU - Li Z AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China. FAU - Wang, Ying AU - Wang Y AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China. FAU - He, Long AU - He L AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China. FAU - Guo, Yujia AU - Guo Y AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China. FAU - Zhao, Liting AU - Zhao L AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China. FAU - Xue, Xuting AU - Xue X AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China. FAU - Liu, Hongliang AU - Liu H AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Department of Otolaryngology Head & Neck Surgery, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Department of Cell Biology and Genetics, the Basic Medical School of Shanxi Medical University, Taiyuan 030001, Shanxi, China. Electronic address: liuhl2018@sxent.org. FAU - Zhang, Chunming AU - Zhang C AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Department of Otolaryngology Head & Neck Surgery, First Hospital of Shanxi Medical University, Taiyuan 030001, China. Electronic address: zcmsxmu@sxent.org. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231202 PL - England TA - Cell Signal JT - Cellular signalling JID - 8904683 RN - W7IBY2BGAX (6-methyladenine) RN - 0 (MicroRNAs) RN - EC 3.6.1.- (EIF4A3 protein, human) RN - EC 2.7.7.- (Eukaryotic Initiation Factor-4A) RN - EC 3.6.4.13 (DEAD-box RNA Helicases) RN - 0 (YTHDF1 protein, human) RN - 0 (RNA-Binding Proteins) SB - IM MH - Humans MH - Squamous Cell Carcinoma of Head and Neck MH - *Carcinoma, Squamous Cell/pathology MH - *Laryngeal Neoplasms/genetics/metabolism MH - Cell Proliferation/genetics MH - Cell Line, Tumor MH - *Head and Neck Neoplasms MH - Gene Expression Regulation, Neoplastic MH - *MicroRNAs/metabolism MH - Eukaryotic Initiation Factor-4A/genetics/metabolism MH - DEAD-box RNA Helicases/metabolism MH - RNA-Binding Proteins/metabolism OTO - NOTNLM OT - EIF4A3 OT - EMT OT - Laryngeal squamous cell carcinoma OT - YTHDF1 OT - m6A COIS- Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Huina Guo reports financial support, article publishing charges, equipment, drugs, or supplies, statistical analysis, and writing assistance were provided by Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University. Qi Han reports financial support, statistical analysis, and writing assistance were provided by Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University. Xiaoya Guan reports statistical analysis was provided by Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University. Zhongxun Li reports financial support and writing assistance were provided by Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University. Ying Wang reports equipment, drugs, or supplies and writing assistance were provided by Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University. Long He reports financial support and equipment, drugs, or supplies were provided by Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University. Yujia Guo reports equipment, drugs, or supplies was provided by Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University. Liting Zhao reports equipment, drugs, or supplies was provided by Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University. Xuting Xue reports financial support and equipment, drugs, or supplies were provided by Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University. Hongliang Liu reports financial support, statistical analysis, and writing assistance were provided by Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University. Chunming Zhang reports administrative support and writing assistance were provided by Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University. EDAT- 2023/12/05 00:41 MHDA- 2024/01/02 11:43 CRDT- 2023/12/04 19:21 PHST- 2023/09/27 00:00 [received] PHST- 2023/11/09 00:00 [revised] PHST- 2023/12/01 00:00 [accepted] PHST- 2024/01/02 11:43 [medline] PHST- 2023/12/05 00:41 [pubmed] PHST- 2023/12/04 19:21 [entrez] AID - S0898-6568(23)00417-5 [pii] AID - 10.1016/j.cellsig.2023.111002 [doi] PST - ppublish SO - Cell Signal. 2024 Feb;114:111002. doi: 10.1016/j.cellsig.2023.111002. Epub 2023 Dec 2.