PMID- 38063205
OWN - NLM
STAT- MEDLINE
DCOM- 20240110
LR  - 20240110
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 64
IP  - 2
DP  - 2024 Feb
TI  - m(6)A‑modified HOXC10 promotes HNSCC progression via co‑activation of ADAM17/EGFR 
      and Wnt/beta‑catenin signaling.
LID - 10 [pii]
LID - 10.3892/ijo.2023.5598 [doi]
AB  - The homeobox (HOX) gene family plays a fundamental role in carcinogenesis. 
      However, the oncogenic mechanism of HOXC10 in head and neck squamous cell 
      carcinoma (HNSCC) remains unclear. In the present study, it was revealed that 
      HOXC10 expression was significantly higher in HNSCC tissues than in adjacent 
      tissues, and a high level of HOXC10 was closely associated with worse clinical 
      outcomes. HOXC10 overexpression promoted HNSCC cell proliferation, migration, and 
      invasion, both in vitro and in vivo. Mechanistically, chromatin 
      immunoprecipitation sequencing revealed that HOXC10 drove the transcriptional 
      activation of a disintegrin and metalloproteinase 17 (ADAM17), and the 
      ADAM17/epidermal growth factor receptor (EGFR)/ERK1/2 signaling pathway 
      facilitating the proliferation of HNSCC. Furthermore, mass spectrometric analysis 
      indicated that HOXC10 interacted with ribosomal protein S15A (RPS15A) and 
      enhanced RPS15A protein expression, activating the Wnt/beta‑catenin pathway and 
      contributing to invasion and metastasis of HNSCC. Additionally, the methylated 
      RNA immune precipitation and RNA antisense purification assays showed that 
      N(6)‑methyladenosine (m(6)A) writer, methyltransferase‑like 3, catalyzed m6A 
      modification of the HOXC10 transcript, m6A reader insulin like growth factor 2 
      mRNA binding protein (IGF2BP)1 and IGF2BP3 involved in recognizing and 
      stabilizing m(6)A‑tagged HOXC10 mRNA. In summary, the present study identified 
      HOXC10 as a promising candidate oncogene in HNSCC. The m(6)A 
      modification‑mediated HOXC10 promoted proliferation, migration, and invasion of 
      HNSCC through co‑activation of ADAM17/EGFR and Wnt/beta‑catenin signaling, providing 
      a novel diagnostic and prognostic biomarker and a potential therapeutic target 
      for HNSCC.
FAU - Zhou, Yujuan
AU  - Zhou Y
AD  - Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, 
      Shanghai 200031, P.R. China.
FAU - Huang, Qiang
AU  - Huang Q
AD  - Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, 
      Shanghai 200031, P.R. China.
FAU - Wu, Chunping
AU  - Wu C
AD  - Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, 
      Shanghai 200031, P.R. China.
FAU - Xu, Ye
AU  - Xu Y
AD  - Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory 
      of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, 
      P.R. China.
FAU - Guo, Yang
AU  - Guo Y
AD  - Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, 
      Shanghai 200031, P.R. China.
FAU - Yuan, Xiaohui
AU  - Yuan X
AD  - Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, 
      Shanghai 200031, P.R. China.
FAU - Xu, Chengzhi
AU  - Xu C
AD  - Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, 
      Shanghai 200031, P.R. China.
FAU - Zhou, Liang
AU  - Zhou L
AD  - Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, 
      Shanghai 200031, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20231208
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (ADAM17 protein, human)
RN  - 0 (beta Catenin)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (HOXC10 protein, human)
RN  - 63231-63-0 (RNA)
RN  - 0 (RNA, Messenger)
RN  - CLE6G00625 (N-methyladenosine)
SB  - IM
MH  - Humans
MH  - *ADAM17 Protein/genetics
MH  - beta Catenin/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - ErbB Receptors/genetics/metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - *Genes, Homeobox
MH  - *Head and Neck Neoplasms/genetics
MH  - *Homeodomain Proteins/metabolism
MH  - RNA
MH  - RNA, Messenger
MH  - Squamous Cell Carcinoma of Head and Neck/genetics
MH  - Wnt Signaling Pathway/genetics
MH  - RNA Methylation
PMC - PMC10734666
OTO - NOTNLM
OT  - N6‑methyladenosine
OT  - a disintegrin and metalloproteinase 17
OT  - head and neck squamous cell carcinoma
OT  - homeobox C10
OT  - ribosomal protein S15A
COIS- The authors declare that they have no competing interests.
EDAT- 2023/12/08 12:42
MHDA- 2023/12/17 13:19
PMCR- 2023/12/06
CRDT- 2023/12/08 07:45
PHST- 2023/07/25 00:00 [received]
PHST- 2023/10/12 00:00 [accepted]
PHST- 2023/12/17 13:19 [medline]
PHST- 2023/12/08 12:42 [pubmed]
PHST- 2023/12/08 07:45 [entrez]
PHST- 2023/12/06 00:00 [pmc-release]
AID - 10 [pii]
AID - ijo-64-02-05598 [pii]
AID - 10.3892/ijo.2023.5598 [doi]
PST - ppublish
SO  - Int J Oncol. 2024 Feb;64(2):10. doi: 10.3892/ijo.2023.5598. Epub 2023 Dec 8.