Down-Regulation of MiR-181c-5p Promotes Epithelial-to-Mesenchymal Transition in Laryngeal Squamous Cell Carcinoma via Targeting SERPINE1

被引:14
作者
Li, Xin [1 ,2 ,3 ]
Wu, Ping [1 ,2 ,3 ]
Tang, Yaoyun [1 ,2 ,3 ]
Fan, Yuhua [1 ,2 ,3 ]
Liu, Yalan [1 ,2 ,3 ]
Fang, Xing [1 ,2 ,3 ]
Wang, Wei [1 ,2 ,3 ]
Zhao, Suping [1 ,2 ,3 ]
机构
[1] Cent South Univ, Dept Otorhinolaryngol Head & Neck Surg, Xiangya Hosp, Changsha, Peoples R China
[2] Cent South Univ, Prov Key Lab Otolaryngol Crit Dis, Xiangya Hosp, Changsha, Peoples R China
[3] Cent South Univ, Natl Clin Res Ctr Geriatr Disorders, Xiangya Hosp, Changsha, Peoples R China
基金
中国国家自然科学基金;
关键词
miRNA; mRNA; laryngeal squamous cell carcinoma; epithelial-to-mesenchymal transition; biomarker; HEAD; MICRORNAS; EXPRESSION; TUMOR; PROLIFERATION; METASTASIS; INVASION;
D O I
10.3389/fonc.2020.544476
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Laryngeal squamous cell carcinoma (LSCC) arises from the squamous epithelium of the larynx and is associated with a high incidence of cervical lymph node metastasis. MicroRNAs (miRNAs) play a crucial role in the epigenetic regulation of cellular biological processes, including cancer metastasis. However, the molecular mechanisms of specific miRNAs responsible for LSCC metastasis and their clinical significance have yet to be fully elucidated. In this study, LSCC cohort datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were downloaded and examined by comprehensive bioinformatics analysis, which revealed that upregulation of mRNA SERPINE1 and downregulation of miR-181c-5p were associated with unfavorable overall survival. Our analysis showed that SERPINE1 expression negatively correlated with the expression level of miR-181c-5p in our LSCC patient samples. Silencing of miR-181c-5p expression promoted cell migration and invasion in cell lines, whereas the overexpression of miR-181c-5p suppressed cell migration and epithelial-to-mesenchymal transition (EMT) through the downregulation of SERPINE1. Further analysis showed that the enhancement effect on EMT and metastasis induced by silencing miR-181c-5p could be rescued through knockdown of SERPINE1 expression in vitro. Collectively, our findings indicated that miR-181c-5p acted as an EMT suppressor miRNA by downregulation of SERPINE1 in LSCC and offers novel strategies for the prevention of metastasis in LSCC.
引用
收藏
页数:14
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共 46 条
[1]   TP53/miR-34a-associated signaling targets SERPINE1 expression in human pancreatic cancer [J].
Akula, Shaw M. ;
Ruvolo, Peter P. ;
McCubrey, James A. .
AGING-US, 2020, 12 (03) :2777-2797
[2]   EMT: 2016 [J].
Angela Nieto, M. ;
Huang, Ruby Yun-Ju ;
Jackson, Rebecca A. ;
Thiery, Jean Paul .
CELL, 2016, 166 (01) :21-45
[3]   Effect of serpinE1 overexpression on the primary tumor and lymph node, and lung metastases in head and neck squamous cell carcinoma [J].
Arroyo-Solera, Irene ;
Angel Pavon, Miguel ;
Leon, Xavier ;
Lopez, Montserrat ;
Gallardo, Alberto ;
Virtudes Cespedes, Maria ;
Casanova, Isolda ;
Pallares, Victor ;
Lopez-Pousa, Antonio ;
Antonia Mangues, Maria ;
Barnadas, Agusti ;
Quer, Miquel ;
Mangues, Ramon .
HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, 2019, 41 (02) :429-439
[4]   Hypoxia-induced reactive oxygen species mediate N-cadherin and SERPINE1 expression, EGFR signalling and motility in MDA-MB-468 breast cancer cells [J].
Azimi, Iman ;
Petersen, Rosalie M. ;
Thompson, Erik W. ;
Roberts-Thomson, Sarah J. ;
Monteith, Gregory R. .
SCIENTIFIC REPORTS, 2017, 7
[5]   MicroRNAs in Oncogenesis and Tumor Suppression [J].
Barbato, Simona ;
Solaini, Giancarlo ;
Fabbri, Muller .
MIRNAS IN DIFFERENTIATION AND DEVELOPMENT, 2017, 333 :229-268
[6]   uPAR: A versatile signalling orchestrator [J].
Blasi, F ;
Carmeliet, P .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2002, 3 (12) :932-943
[7]   MicroRNA signatures in human cancers [J].
Calin, George A. ;
Croce, Carlo M. .
NATURE REVIEWS CANCER, 2006, 6 (11) :857-866
[8]   Upregulation of microRNA-141 suppresses epithelial-mesenchymal transition and lymph node metastasis in laryngeal cancer through HOXC6-dependent TGF-β signaling pathway [J].
Chen, Li ;
Sun, De-Zhong ;
Fu, Yu-Gui ;
Yang, Pei-Zhen ;
Lv, Huai-Qing ;
Gao, Yongli ;
Zhang, Xiao-Yan .
CELLULAR SIGNALLING, 2020, 66
[9]   AGR3 promotes the sternness of colorectal cancer via modulating Wnt/β-catenin signalling [J].
Chi, Jiangyang ;
Zhang, Hongyan ;
Hu, Jia ;
Song, Yu ;
Li, Jing ;
Wang, Lin ;
Wang, Zheng .
CELLULAR SIGNALLING, 2020, 65
[10]   Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients [J].
de Jong, Monique C. ;
ten Hoeve, Jelle J. ;
Grenman, Reidar ;
Wessels, Lodewyk F. ;
Kerkhoven, Ron ;
te Riele, Hein ;
van den Brekel, Michiel W. M. ;
Verheij, Marcel ;
Begg, Adrian C. .
CLINICAL CANCER RESEARCH, 2015, 21 (24) :5630-5638