Promoter Methylation-Regulated miR-145-5p Inhibits Laryngeal Squamous Cell Carcinoma Progression by Targeting FSCN1.

Animals Carcinoma, Squamous Cell / genetics Carrier Proteins / genetics Cell Line Cell Line, Tumor DNA Methylation / genetics Female Gene Expression Regulation, Neoplastic / genetics HEK293 Cells Head and Neck Neoplasms / genetics Humans Laryngeal Neoplasms / genetics Male Mice Mice, Inbred BALB C Mice, Nude MicroRNAs / genetics Microfilament Proteins / genetics Promoter Regions, Genetic / genetics
FSCN1 epithelial-mesenchymal transition laryngeal squamous cell carcinoma miR-145-5p promoter methylation

Journal

Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581

Informations de publication

Date de publication:
06 02 2019
Historique:
received: 01 07 2018
revised: 17 09 2018
accepted: 20 09 2018
pubmed: 21 10 2018
medline: 18 12 2019
entrez: 21 10 2018
Statut: ppublish

Résumé

Laryngeal squamous cell carcinoma (LSCC) is a common form of head and neck cancer with poor prognosis. However, the mechanism underlying the pathogenesis of LSCC remains unclear. Here, we demonstrated increased expression of fascin actin-bundling protein 1 (FSCN1) and decreased expression of microRNA-145-5p (miR-145-5p) in a clinical cohort of LSCC. Luciferase assay revealed that miR-145-5p is a negative regulator of FSCN1. Importantly, low miR-145-5p expression was correlated with TNM (tumor, node, metastasis) status and metastasis. Moreover, cases with low miR-145-5p/high FSCN1 expression showed poor prognosis, and these characteristics together served as independent prognostic indicators of survival. Gain- and loss-of-function studies showed that miR-145-5p overexpression or FSCN1 knockdown inhibited LSCC migration, invasion, and growth by suppressing the epithelial-mesenchymal transition along with inducing cell-cycle arrest and apoptosis. Additionally, hypermethylation of the miR-145-5p promoter suggested that repression of miR-145-5p arises through epigenetic inactivation. LSCC tumor growth in vivo could be inhibited by using miR-145-5p agomir or FSCN1 small interfering RNA (siRNA), which highlights the potential for clinical translation. Collectively, our findings indicate that miR-145-5p plays critical roles in inhibiting the progression of LSCC by suppressing FSCN1. Both miR-145-5p and FSCN1 are important potential prognostic markers and therapeutic targets for LSCC.

Identifiants

DOI: 10.1016/j.ymthe.2018.09.018 PMID: 30341010 PMC: PMC6369713
pubmed: 30341010
pii: S1525-0016(18)30459-3
doi: 10.1016/j.ymthe.2018.09.018
pmc: PMC6369713
pii:
doi:

Substances chimiques

Carrier Proteins 0
FSCN1 protein, human 0
MIRN145 microRNA, human 0
MicroRNAs 0
Microfilament Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

365-379

Informations de copyright

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

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Auteurs

Wei Gao (W)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Chunming Zhang (C)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Wenqi Li (W)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Huizheng Li (H)

Department of Otolaryngology Head & Neck Surgery, Dalian Municipal Friendship Hospital, Dalian 116100, Liaoning, China.

Jiangwei Sang (J)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Qinli Zhao (Q)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Yunfeng Bo (Y)

Department of Pathology, Shanxi Cancer Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China.

Hongjie Luo (H)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Xiwang Zheng (X)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Yan Lu (Y)

Department of Otolaryngology Head & Neck Surgery, The First Hospital, Jinzhou Medical University, Jinzhou 121001, Liaoning, China.

Yong Shi (Y)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Dongli Yang (D)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Ruiping Zhang (R)

The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China; Department of MRI & CT, Shanxi Cancer Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China.

Zhenyu Li (Z)

The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China; Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030001, Shanxi, China.

Jiajia Cui (J)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Yuliang Zhang (Y)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Min Niu (M)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Jun Li (J)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Zhongqiang Wu (Z)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Huina Guo (H)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Caixia Xiang (C)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Juan Wang (J)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Juan Hou (J)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Lu Zhang (L)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China.

Rick F Thorne (RF)

Translational Research Institute, Henan Provincial People's Hospital, School of Medicine, Henan University, Zhengzhou 450053, Henan, China; School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia. Electronic address: rickfthorne@gmail.com.

Yongping Cui (Y)

Translational Medicine Research Center, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi, China. Electronic address: cuiyp@sxmu.edu.cn.

Yongyan Wu (Y)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China. Electronic address: wuyongyan@sxent.org.

Shuxin Wen (S)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China. Electronic address: wsxsx@sxent.org.

Binquan Wang (B)

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, Shanxi, China; Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan 030001, Shanxi, China; The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, China. Electronic address: wbq_xy@sxent.org.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Promoter Methylation-Regulated miR-145-5p...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs épithéliales épidermoïdes et glandulaires › Tumeurs épidermoïdes › Carcinome épidermoïde › Promoter Methylation-Regulated miR-145-5p...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de transport › Promoter Methylation-Regulated miR-145-5p...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Promoter Methylation-Regulated miR-145-5p...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Promoter Methylation-Regulated miR-145-5p...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Promoter Methylation-Regulated miR-145-5p...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Promoter Methylation-Regulated miR-145-5p...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › Promoter Methylation-Regulated miR-145-5p...
questionsmedicales.fr › Tumeurs › Tumeurs par siège › Tumeurs de la tête et du cou › Promoter Methylation-Regulated miR-145-5p...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Promoter Methylation-Regulated miR-145-5p...
questionsmedicales.fr › Maladies oto-rhino-laryngologiques › Tumeurs oto-rhino-laryngologiques › Tumeurs du larynx › Promoter Methylation-Regulated miR-145-5p...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Promoter Methylation-Regulated miR-145-5p...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée BALB C › Promoter Methylation-Regulated miR-145-5p...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souches mutantes de souris › Souris nude › Promoter Methylation-Regulated miR-145-5p...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › microARN › Promoter Methylation-Regulated miR-145-5p...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cytosquelette › Protéines des microfilaments › Promoter Methylation-Regulated miR-145-5p...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Éléments de régulation transcriptionnelle › Régions promotrices (génétique) › Promoter Methylation-Regulated miR-145-5p...