PMID- 38369001
OWN - NLM
STAT- MEDLINE
DCOM- 20240326
LR  - 20240326
IS  - 1872-7980 (Electronic)
IS  - 0304-3835 (Linking)
VI  - 587
DP  - 2024 Apr 10
TI  - m6A/HOXA10-AS/ITGA6 axis aggravates oxidative resistance and malignant 
      progression of laryngeal squamous cell carcinoma through regulating Notch and 
      Keap1/Nrf2 pathways.
PG  - 216735
LID - S0304-3835(24)00128-9 [pii]
LID - 10.1016/j.canlet.2024.216735 [doi]
AB  - As the second most prevalent malignant tumor of head and neck, laryngeal squamous 
      cell carcinoma (LSCC) imposes a substantial health burden on patients worldwide. 
      Within recent years, resistance to oxidative stress and N6-methyladenosine (m6A) 
      of RNA have been proved to be significantly involved in tumorigenesis. In current 
      study, we investigated the oncogenic role of m6A modified long non coding RNAs 
      (lncRNAs), specifically HOXA10-AS, and its downstream signaling pathway in the 
      regulation of oxidative resistance in LSCC. Bioinformatics analysis revealed that 
      heightened expression of HOXA10-AS was associated with the poor prognosis in LSCC 
      patients, and N (6)-Methyladenosine (m6A) methyltransferase-like 3 (METTL3) was 
      identified as a factor in promoting m6A modification of HOXA10-AS and further 
      intensify its RNA stability. Mechanistically, HOXA10-AS was found to play as a 
      competitive endogenous RNA (ceRNA) by sequestering miR-29 b-3p and preventing its 
      downregulation of Integrin subunit alpha 6 (ITGA6), ultimately enhancing the 
      oxidative resistance of tumor cells and promoting the malignant progression of 
      LSCC. Furthermore, our research elucidated the mechanism by which ITGA6 
      accelerates Keap1 proteasomal degradation via enhancing TRIM25 expression, 
      leading to increased Nrf2 stability and exacerbating its aberrant activation. 
      Additionally, we demonstrated that ITGA6 enhances gamma-secretase-mediated Notch 
      signaling activation, ultimately promoting RBPJ-induced TRIM25 transcription. The 
      current study provides the evidence supporting the effect of m6A modified 
      HOXA10-AS and its downstream miR-29 b-3p/ITGA6 axis on regulating oxidative 
      resistance and malignant progression in LSCC through the Notch and Keap1/Nrf2 
      pathways, and proposed that targeting this axis holds promise as a potential 
      therapeutic approach for treating LSCC.
CI  - Copyright (c) 2024 Elsevier B.V. All rights reserved.
FAU - Zhao, Kai
AU  - Zhao K
AD  - Department of Otolaryngology Head and Neck Surgery, Hainan Hospital of Chinese 
      PLA General Hospital, Sanya, 572013, PR China.
FAU - Chen, Liwei
AU  - Chen L
AD  - Department of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, 
      Beijing 100853, PR China.
FAU - Xie, Yingli
AU  - Xie Y
AD  - Department of Otolaryngology Head and Neck Surgery, Hainan Hospital of Chinese 
      PLA General Hospital, Sanya, 572013, PR China; Medical School of Chinese PLA, 
      Beijing, 100853, PR China.
FAU - Ren, Nan
AU  - Ren N
AD  - Department of Otolaryngology Head and Neck Surgery, Hainan Hospital of Chinese 
      PLA General Hospital, Sanya, 572013, PR China.
FAU - Li, Jianhui
AU  - Li J
AD  - Department of Otolaryngology Head and Neck Surgery, Hainan Hospital of Chinese 
      PLA General Hospital, Sanya, 572013, PR China.
FAU - Zhai, Xingyou
AU  - Zhai X
AD  - Department of Otolaryngology Head and Neck Surgery, Hainan Hospital of Chinese 
      PLA General Hospital, Sanya, 572013, PR China.
FAU - Zheng, Shikang
AU  - Zheng S
AD  - Department of Otolaryngology Head and Neck Surgery, Hainan Hospital of Chinese 
      PLA General Hospital, Sanya, 572013, PR China.
FAU - Liu, Kun
AU  - Liu K
AD  - Department of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, 
      Beijing 100853, PR China.
FAU - Wang, Cheng
AU  - Wang C
AD  - Department of Otolaryngology Head and Neck Surgery, Hainan Hospital of Chinese 
      PLA General Hospital, Sanya, 572013, PR China.
FAU - Qiu, Qibing
AU  - Qiu Q
AD  - The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 
      510515, PR China.
FAU - Peng, Xin
AU  - Peng X
AD  - Department of Otolaryngology Head and Neck Surgery, Hainan Hospital of Chinese 
      PLA General Hospital, Sanya, 572013, PR China.
FAU - Wang, Wenjia
AU  - Wang W
AD  - Department of Otolaryngology Head and Neck Surgery, Hainan Hospital of Chinese 
      PLA General Hospital, Sanya, 572013, PR China; Medical School of Chinese PLA, 
      Beijing, 100853, PR China.
FAU - Liu, Jinjing
AU  - Liu J
AD  - Medical School of Chinese PLA, Beijing, 100853, PR China.
FAU - Che, Qin
AU  - Che Q
AD  - Department of Otolaryngology Head and Neck Surgery, Hainan Hospital of Chinese 
      PLA General Hospital, Sanya, 572013, PR China.
FAU - Fan, Junda
AU  - Fan J
AD  - Department of Otolaryngology Head and Neck Surgery, Hainan Hospital of Chinese 
      PLA General Hospital, Sanya, 572013, PR China.
FAU - Hu, Hai
AU  - Hu H
AD  - Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, 510120, PR China; Guangdong Provincial Key Laboratory of Malignant 
      Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, 510120, PR China. Electronic address: 
      huhai@mail.sysu.edu.cn.
FAU - Liu, Mingbo
AU  - Liu M
AD  - Department of Otolaryngology Head and Neck Surgery, Hainan Hospital of Chinese 
      PLA General Hospital, Sanya, 572013, PR China; Department of Otolaryngology Head 
      and Neck Surgery, Chinese PLA General Hospital, Beijing 100853, PR China; The 
      Second School of Clinical Medicine, Southern Medical University, Guangzhou, 
      510515, PR China. Electronic address: mingbo666@vip.163.com.
LA  - eng
PT  - Journal Article
DEP - 20240217
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (MicroRNAs)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - W7IBY2BGAX (6-methyladenine)
RN  - 0 (RNA, Long Noncoding)
RN  - EC 2.1.1.62 (METTL3 protein, human)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - 140441-81-2 (HOXA10 protein, human)
RN  - 0 (ITGA6 protein, human)
RN  - 0 (Homeobox A10 Proteins)
RN  - JAC85A2161 (Adenine)
RN  - 0 (Integrin alpha6)
SB  - IM
MH  - Humans
MH  - Squamous Cell Carcinoma of Head and Neck/genetics
MH  - *MicroRNAs/genetics
MH  - NF-E2-Related Factor 2/genetics/metabolism
MH  - *Laryngeal Neoplasms/genetics/metabolism/pathology
MH  - *Carcinoma, Squamous Cell/genetics
MH  - Kelch-Like ECH-Associated Protein 1/genetics/metabolism
MH  - *Head and Neck Neoplasms/genetics
MH  - Oxidative Stress
MH  - Cell Line, Tumor
MH  - Gene Expression Regulation, Neoplastic
MH  - Cell Proliferation
MH  - *RNA, Long Noncoding/genetics
MH  - Methyltransferases/metabolism
MH  - *Homeobox A10 Proteins
MH  - Adenine/*analogs & derivatives
MH  - *Integrin alpha6
OTO - NOTNLM
OT  - HOXA10-AS
OT  - LSCC
OT  - Notch
OT  - Nrf2
OT  - m6A
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2024/02/19 00:42
MHDA- 2024/03/26 06:45
CRDT- 2024/02/18 19:14
PHST- 2023/12/09 00:00 [received]
PHST- 2024/02/05 00:00 [revised]
PHST- 2024/02/16 00:00 [accepted]
PHST- 2024/03/26 06:45 [medline]
PHST- 2024/02/19 00:42 [pubmed]
PHST- 2024/02/18 19:14 [entrez]
AID - S0304-3835(24)00128-9 [pii]
AID - 10.1016/j.canlet.2024.216735 [doi]
PST - ppublish
SO  - Cancer Lett. 2024 Apr 10;587:216735. doi: 10.1016/j.canlet.2024.216735. Epub 2024 
      Feb 17.