PMID- 30341010
OWN - NLM
STAT- MEDLINE
DCOM- 20191216
LR  - 20220408
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 27
IP  - 2
DP  - 2019 Feb 6
TI  - Promoter Methylation-Regulated miR-145-5p Inhibits Laryngeal Squamous Cell 
      Carcinoma Progression by Targeting FSCN1.
PG  - 365-379
LID - S1525-0016(18)30459-3 [pii]
LID - 10.1016/j.ymthe.2018.09.018 [doi]
AB  - 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.
CI  - Copyright (c) 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Gao, Wei
AU  - Gao W
AD  - 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.
FAU - Zhang, Chunming
AU  - Zhang C
AD  - 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.
FAU - Li, Wenqi
AU  - Li W
AD  - 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.
FAU - Li, Huizheng
AU  - Li H
AD  - Department of Otolaryngology Head & Neck Surgery, Dalian Municipal Friendship 
      Hospital, Dalian 116100, Liaoning, China.
FAU - Sang, Jiangwei
AU  - Sang J
AD  - 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.
FAU - Zhao, Qinli
AU  - Zhao Q
AD  - 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.
FAU - Bo, Yunfeng
AU  - Bo Y
AD  - Department of Pathology, Shanxi Cancer Hospital, Shanxi Medical University, 
      Taiyuan 030001, Shanxi, China.
FAU - Luo, Hongjie
AU  - Luo H
AD  - 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.
FAU - Zheng, Xiwang
AU  - Zheng X
AD  - 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.
FAU - Lu, Yan
AU  - Lu Y
AD  - Department of Otolaryngology Head & Neck Surgery, The First Hospital, Jinzhou 
      Medical University, Jinzhou 121001, Liaoning, China.
FAU - Shi, Yong
AU  - Shi Y
AD  - 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.
FAU - Yang, Dongli
AU  - Yang D
AD  - 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.
FAU - Zhang, Ruiping
AU  - Zhang R
AD  - 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.
FAU - Li, Zhenyu
AU  - Li Z
AD  - 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.
FAU - Cui, Jiajia
AU  - Cui J
AD  - 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.
FAU - Zhang, Yuliang
AU  - Zhang Y
AD  - 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.
FAU - Niu, Min
AU  - Niu M
AD  - 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.
FAU - Li, Jun
AU  - Li J
AD  - 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.
FAU - Wu, Zhongqiang
AU  - Wu Z
AD  - 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.
FAU - Guo, Huina
AU  - Guo H
AD  - 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.
FAU - Xiang, Caixia
AU  - Xiang C
AD  - 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.
FAU - Wang, Juan
AU  - Wang J
AD  - 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.
FAU - Hou, Juan
AU  - Hou J
AD  - 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.
FAU - Zhang, Lu
AU  - Zhang L
AD  - 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.
FAU - Thorne, Rick F
AU  - Thorne RF
AD  - 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.
FAU - Cui, Yongping
AU  - Cui Y
AD  - 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.
FAU - Wu, Yongyan
AU  - Wu Y
AD  - 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.
FAU - Wen, Shuxin
AU  - Wen S
AD  - 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.
FAU - Wang, Binquan
AU  - Wang B
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180927
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Carrier Proteins)
RN  - 0 (FSCN1 protein, human)
RN  - 0 (MIRN145 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Microfilament Proteins)
SB  - IM
MH  - Animals
MH  - Carcinoma, Squamous Cell/genetics/metabolism
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - DNA Methylation/genetics/*physiology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/genetics/physiology
MH  - HEK293 Cells
MH  - Head and Neck Neoplasms/*genetics/*metabolism
MH  - Humans
MH  - Laryngeal Neoplasms/*genetics/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - MicroRNAs/*genetics/physiology
MH  - Microfilament Proteins/genetics/*metabolism
MH  - Promoter Regions, Genetic/*genetics
PMC - PMC6369713
OTO - NOTNLM
OT  - FSCN1
OT  - epithelial-mesenchymal transition
OT  - laryngeal squamous cell carcinoma
OT  - miR-145-5p
OT  - promoter methylation
EDAT- 2018/10/21 06:00
MHDA- 2019/12/18 06:00
PMCR- 2020/02/06
CRDT- 2018/10/21 06:00
PHST- 2018/07/01 00:00 [received]
PHST- 2018/09/17 00:00 [revised]
PHST- 2018/09/20 00:00 [accepted]
PHST- 2018/10/21 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2018/10/21 06:00 [entrez]
PHST- 2020/02/06 00:00 [pmc-release]
AID - S1525-0016(18)30459-3 [pii]
AID - 10.1016/j.ymthe.2018.09.018 [doi]
PST - ppublish
SO  - Mol Ther. 2019 Feb 6;27(2):365-379. doi: 10.1016/j.ymthe.2018.09.018. Epub 2018 
      Sep 27.