Format

Send to

Choose Destination
Mol Ther. 2019 Feb 6;27(2):365-379. doi: 10.1016/j.ymthe.2018.09.018. Epub 2018 Sep 27.

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

Author information

1
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.
2
Department of Otolaryngology Head & Neck Surgery, Dalian Municipal Friendship Hospital, Dalian 116100, Liaoning, China.
3
Department of Pathology, Shanxi Cancer Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
4
Department of Otolaryngology Head & Neck Surgery, The First Hospital, Jinzhou Medical University, Jinzhou 121001, Liaoning, China.
5
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.
6
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.
7
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.
8
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.
9
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.
10
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.
11
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.

Abstract

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.

KEYWORDS:

FSCN1; epithelial-mesenchymal transition; laryngeal squamous cell carcinoma; miR-145-5p; promoter methylation

PMID:
30341010
PMCID:
PMC6369713
[Available on 2020-02-06]
DOI:
10.1016/j.ymthe.2018.09.018
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center