PMID- 37536262
OWN - NLM
STAT- MEDLINE
DCOM- 20230908
LR  - 20230908
IS  - 1532-3072 (Electronic)
IS  - 0040-8166 (Linking)
VI  - 84
DP  - 2023 Oct
TI  - ZC3H13 reduced DUOX1-mediated ferroptosis in laryngeal squamous cell carcinoma 
      cells through m6A-dependent modification.
PG  - 102187
LID - S0040-8166(23)00175-1 [pii]
LID - 10.1016/j.tice.2023.102187 [doi]
AB  - Laryngeal squamous cell carcinoma (LSCC) is the second most common head and neck 
      cancer. To identify the link between ferroptosis and LSCC, we targeted the dual 
      oxidase 1 (DUOX1) gene. This study aimed to reveal the intrinsic mechanism by 
      which the DUOX1-zinc-finger CCCH domain-containing protein 13 (ZC3H13) 
      ferroptosis axis affected the LSCC process. GEPIA was used to investigate the 
      expression of DUOX1 in LSCC, and the expression levels of DUOX1 and ZC3H13 were 
      manipulated by overexpression and RNA interference. MTT assay was used to detect 
      cell proliferation. Chromatin immunoprecipitation (CHIP) detected the binding of 
      DUOX1 and ZC3H13, and ROS assessment and intracellular Fe(2+) content 
      determination were performed to examine the ferroptosis. MeRIP was used to 
      analyze the m6A methylation of DUOX1. Ferroptosis-related proteins were detected 
      by qRT-PCR. DUOX1 was found to be poorly expressed in LSCC cells, low DUOX1 level 
      promoted LSCC cell proliferation, and low ZC3H13 level decreased LSCC cell 
      proliferation. Besides, there was an interaction between DUOX1 and ZC3H13. DUOX1 
      could inhibit the expression levels of ferroptosis-related genes GPX4 and F1H1 in 
      LSCC cells DUOX1 inhibited the expression levels of ROS and ferroptosis-related 
      genes GPX4 and F1H1 and increased intracellular iron content in LSCC cells, but 
      ZC3H13 reversed this phenomenon by inhibiting DUOX1 gene through m6A methylation 
      modification. ZC3H13 reduced DUOX1-mediated ferroptosis in LSCC cells through 
      m6A-dependent modification. The regulatory pathway of DUOX1 and ferroptosis are 
      potential targets for designing diagnostic and combination therapeutic strategies 
      for LSCC patients.
CI  - Copyright (c) 2023 Elsevier Ltd. All rights reserved.
FAU - Huang, Lili
AU  - Huang L
AD  - Department of Otorhinolaryngology, The First People's Hospital of Fuyang 
      Hangzhou, 311400 Hangzhou, Zhejiang Province, China.
FAU - Chen, Guangli
AU  - Chen G
AD  - Department of Otorhinolaryngology, The First People's Hospital of Fuyang 
      Hangzhou, 311400 Hangzhou, Zhejiang Province, China.
FAU - He, Jing
AU  - He J
AD  - Department of Otorhinolaryngology, The First People's Hospital of Fuyang 
      Hangzhou, 311400 Hangzhou, Zhejiang Province, China.
FAU - Wang, Pu
AU  - Wang P
AD  - Department of Otorhinolaryngology, The First People's Hospital of Fuyang 
      Hangzhou, 311400 Hangzhou, Zhejiang Province, China. Electronic address: 
      wangpu_wpu@163.com.
LA  - eng
PT  - Journal Article
DEP - 20230729
PL  - Scotland
TA  - Tissue Cell
JT  - Tissue & cell
JID - 0214745
RN  - EC 1.11.1.- (Dual Oxidases)
RN  - EC 1.6.3.1 (DUOX1 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (ZC3H13 protein, human)
SB  - IM
MH  - Humans
MH  - *Carcinoma, Squamous Cell/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Dual Oxidases/genetics/metabolism
MH  - *Ferroptosis/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - *Head and Neck Neoplasms
MH  - *Laryngeal Neoplasms/metabolism
MH  - Nuclear Proteins/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - RNA-Binding Proteins/genetics
MH  - *Squamous Cell Carcinoma of Head and Neck/genetics
OTO - NOTNLM
OT  - Acyl-CoA synthetase long chain family member 4
OT  - Dual oxidase 1
OT  - Ferritin heavy chain-1
OT  - Ferroptosis
OT  - GPX4
OT  - Laryngeal squamous cell carcinoma
OT  - Methylation
OT  - Nicotinamide adenine dinucleotide phosphate oxidase-1
OT  - Proliferation
OT  - Zinc-finger CCCH domain-containing protein 13
COIS- Declaration of Competing Interest The authors declare no conflicts of interest.
EDAT- 2023/08/04 01:07
MHDA- 2023/09/04 06:42
CRDT- 2023/08/03 18:11
PHST- 2023/06/15 00:00 [received]
PHST- 2023/07/27 00:00 [revised]
PHST- 2023/07/28 00:00 [accepted]
PHST- 2023/09/04 06:42 [medline]
PHST- 2023/08/04 01:07 [pubmed]
PHST- 2023/08/03 18:11 [entrez]
AID - S0040-8166(23)00175-1 [pii]
AID - 10.1016/j.tice.2023.102187 [doi]
PST - ppublish
SO  - Tissue Cell. 2023 Oct;84:102187. doi: 10.1016/j.tice.2023.102187. Epub 2023 Jul 
      29.