PMID- 38489902
OWN - NLM
STAT- MEDLINE
DCOM- 20240329
LR  - 20240329
IS  - 1090-2414 (Electronic)
IS  - 0147-6513 (Linking)
VI  - 274
DP  - 2024 Apr 1
TI  - Nicotine downregulates miR-375-3p via neurotrophic tyrosine receptor kinase 2 to 
      enhance the malignant behaviors of laryngopharyngeal squamous epithelial cells.
PG  - 116215
LID - S0147-6513(24)00291-4 [pii]
LID - 10.1016/j.ecoenv.2024.116215 [doi]
AB  - Nicotine exposure from smoking constitutes a significant global public health 
      concern. Furthermore, smoking represents a pivotal risk factor for head and neck 
      squamous cell carcinoma (HNSCC). However, the influence of nicotine on HNSCC 
      remains relatively underexplored. Our aim was to unravel the molecular mechanisms 
      that underlie the effect of nicotine on the metastatic cascade of HNSCC. In this 
      study, we discovered a significant association between smoking and HNSCC 
      metastasis and prognosis. Nicotine significantly enhanced HNSCC cell 
      proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) 
      in vitro. Analysis of TCGA-HNSCC and FDEENT-HNSCC cohorts revealed reduced 
      miR-375-3p levels in HNSCC tumor tissues, particularly among current smokers. 
      Additionally, miR-375-3p level was strongly correlated with both lymph node 
      metastasis and tumor stage. By downregulating miR-375-3p, nicotine promotes HNSCC 
      cell metastasis in vitro and hematogenous metastatic capacity in vivo. Utilizing 
      transcriptomic sequencing, molecular docking, dual-luciferase reporter assay, and 
      fluorescence in situ hybridization (FISH), we demonstrated that miR-375-3p 
      specifically binds to 3' untranslated region (3'UTR) of NTRK2 mRNA. Thus, this 
      study uncovers a novel nicotine-induced mechanism involving miR-375-3p-mediated 
      NTRK2 targeting, which promotes HNSCC metastasis. These findings have 
      implications for improving the prognosis of patients with HNSCC, especially in 
      smokers.
CI  - Copyright (c) 2024 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Shen, Yu-Jie
AU  - Shen YJ
AD  - Department of Otorhinolaryngology- Head and Neck Surgery, Eye, Ear, Nose, and 
      Throat Hospital, Fudan University, Shanghai 200031, China.
FAU - Ji, Meng-You
AU  - Ji MY
AD  - Department of Otorhinolaryngology- Head and Neck Surgery, Eye, Ear, Nose, and 
      Throat Hospital, Fudan University, Shanghai 200031, China.
FAU - Huang, Qiang
AU  - Huang Q
AD  - Department of Otorhinolaryngology- Head and Neck Surgery, Eye, Ear, Nose, and 
      Throat Hospital, Fudan University, Shanghai 200031, China.
FAU - Hsueh, Chi-Yao
AU  - Hsueh CY
AD  - Department of Otorhinolaryngology- Head and Neck Surgery, Eye, Ear, Nose, and 
      Throat Hospital, Fudan University, Shanghai 200031, China. Electronic address: 
      hsuehchiyao@gmail.com.
FAU - Du, Huai-Dong
AU  - Du HD
AD  - Department of Otorhinolaryngology- Head and Neck Surgery, Eye, Ear, Nose, and 
      Throat Hospital, Fudan University, Shanghai 200031, China. Electronic address: 
      huaidongd@hotmail.com.
FAU - Zhang, Ming
AU  - Zhang M
AD  - Department of Otorhinolaryngology- Head and Neck Surgery, Eye, Ear, Nose, and 
      Throat Hospital, Fudan University, Shanghai 200031, China. Electronic address: 
      ent_zhm@126.com.
FAU - Zhou, Liang
AU  - Zhou L
AD  - Department of Otorhinolaryngology- Head and Neck Surgery, Eye, Ear, Nose, and 
      Throat Hospital, Fudan University, Shanghai 200031, China. Electronic address: 
      liang.zhou@fdeent.org.
LA  - eng
PT  - Journal Article
DEP - 20240314
PL  - Netherlands
TA  - Ecotoxicol Environ Saf
JT  - Ecotoxicology and environmental safety
JID - 7805381
RN  - 6M3C89ZY6R (Nicotine)
RN  - 0 (tyrosine receptor)
RN  - 0 (MicroRNAs)
RN  - 0 (MIRN375 microRNA, human)
RN  - 0 (Receptors, Amino Acid)
SB  - IM
MH  - Humans
MH  - Squamous Cell Carcinoma of Head and Neck/genetics
MH  - Nicotine/toxicity
MH  - *Carcinoma, Squamous Cell/genetics/metabolism/pathology
MH  - Molecular Docking Simulation
MH  - In Situ Hybridization, Fluorescence
MH  - *Head and Neck Neoplasms/genetics
MH  - *MicroRNAs/genetics
MH  - Epithelial Cells/metabolism
MH  - Cell Line, Tumor
MH  - Gene Expression Regulation, Neoplastic
MH  - Cell Proliferation
MH  - *Receptors, Amino Acid
OTO - NOTNLM
OT  - Head and neck squamous cell carcinoma
OT  - MiR-375-3p
OT  - Neurotrophic tyrosine receptor kinase 2
OT  - Nicotine
OT  - Smoking
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- 2024/03/16 05:42
MHDA- 2024/03/29 06:46
CRDT- 2024/03/15 19:02
PHST- 2023/09/05 00:00 [received]
PHST- 2024/03/01 00:00 [revised]
PHST- 2024/03/12 00:00 [accepted]
PHST- 2024/03/29 06:46 [medline]
PHST- 2024/03/16 05:42 [pubmed]
PHST- 2024/03/15 19:02 [entrez]
AID - S0147-6513(24)00291-4 [pii]
AID - 10.1016/j.ecoenv.2024.116215 [doi]
PST - ppublish
SO  - Ecotoxicol Environ Saf. 2024 Apr 1;274:116215. doi: 10.1016/j.ecoenv.2024.116215. 
      Epub 2024 Mar 14.