MicroRNA-181a suppresses salivary adenoid cystic carcinoma metastasis by targeting MAPK-Snai2 pathway

被引:75
作者
He, Qianting [1 ]
Zhou, Xiaofeng [2 ,3 ]
Li, Su [4 ]
Jin, Yi [2 ]
Chen, Zhujian [2 ,5 ]
Chen, Dan [1 ,2 ]
Cai, Yuchen [4 ]
Liu, Zhonghua [1 ]
Zhao, Tingting [1 ]
Wang, Anxun [1 ]
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Oral & Maxillofacial Surg, Guangzhou 510080, Guangdong, Peoples R China
[2] Univ Illinois, Coll Dent, Ctr Mol Biol Oral Dis, Chicago, IL 60612 USA
[3] Univ Illinois, UIC Canc Ctr, Coll Dent, Dept Periodont, Chicago, IL 60612 USA
[4] Sun Yat Sen Univ, Tumor Hosp, Dept Med, Guangzhou 510060, Guangdong, Peoples R China
[5] Rush Univ, Med Ctr, Dept Anat & Cell Biol, Chicago, IL 60612 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2013年 / 1830卷 / 11期
基金
美国国家卫生研究院;
关键词
MicroRNA; MiR-181a; Salivary adenoid cystic carcinoma; Metastasis; MAPK; Snai2; SQUAMOUS-CELL CARCINOMA; PROMOTES MIGRATION; FAMILY-MEMBERS; HUMAN CANCER; EXPRESSION; INVASION; SLUG; TRANSITION; SIGNATURE; RADIATION;
D O I
10.1016/j.bbagen.2013.07.028
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: To date microRNAs and their contribution to the onset and propagation of salivary adenoid cystic carcinoma (SACC) are limited. The objective of this study was to identify miR-181a and its mechanism in the metastasis of SACC. Methods: At first microarray and quantitative RT-PCR were used to investigate microRNA profiles and miR-181a in paired SACC cell lines with different metastatic potential. Then the effect of miR-181a on metastatic potential of SACC was investigated. MiR-181a target genes and Snai2 promoter activity were investigated using luciferase reporter gene assays. Western blot was used to detect MAPK-Snai2 pathway-related protein level. Results: A panel of deregulated microRNAs (including miR-181a) was identified in paired of SACC cell lines. Functional analysis indicated that miR-181a inhibited SACC cell migration, invasion and proliferation in vitro, and it suppressed tumor growth and lung metastasis in vivo. Direct targeting of miR-181a to MAP2K1, MAPK1 and Snai2 was confirmed by luciferase reporter gene assays. MiR-181a mimic inhibited the expression of MAP2K1, MAPK1 and Snai2 in SACC cells. MAP2K1 or MAPK1 siRNA suppressed Snai2 gene promoter activity and reduced Snai2 expression and the metastatic potential of SACC cells. Conclusions: Our results indicate that miR-181a plays an important role in the metastasis of SACC, and may serve as a novel therapeutic target for SACC. MiR-181a regulates the MAPK-Snai2 pathway both through direct cisregulatory mechanism and through indirect trans-regulatory mechanism. General significance: To our knowledge, this is the first study revealing that miR-181a deregulation mediated the metastasis of SACC by regulating MAPIC-Snai2 pathway. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:5258 / 5266
页数:9
相关论文
共 44 条
[1]   miRNA control of tumor cell invasion and metastasis [J].
Baranwal, Somesh ;
Alahari, Suresh K. .
INTERNATIONAL JOURNAL OF CANCER, 2010, 126 (06) :1283-1290
[2]   Perineural invasion in adenoid cystic carcinoma of the salivary glands: A valid prognostic indicator? [J].
Barrett, A. William ;
Speight, Paul M. .
ORAL ONCOLOGY, 2009, 45 (11) :936-940
[3]   MicroRNA-181a sensitizes human malignant glioma U87MG cells to radiation by targeting Bcl-2 [J].
Chen, Gong ;
Zhu, Wei ;
Shi, Dezhi ;
Lv, Li ;
Zhang, Chun ;
Liu, Ping ;
Hu, Weixing .
ONCOLOGY REPORTS, 2010, 23 (04) :997-1003
[4]   Extracellular Signal-Regulated Kinase Signaling Pathway Regulates Breast Cancer Cell Migration by Maintaining slug Expression [J].
Chen, Haoming ;
Zhu, Genfeng ;
Li, Yong ;
Padia, Ravi N. ;
Dong, Zheng ;
Pan, Zhixing K. ;
Liu, Kebin ;
Huang, Shuang .
CANCER RESEARCH, 2009, 69 (24) :9228-9235
[5]   Down-regulation of the microRNA-99 family members in head and neck squamous cell carcinoma [J].
Chen, Zujian ;
Jin, Yi ;
Yu, Dongsheng ;
Wang, Anxun ;
Mahjabeen, Ishrat ;
Wang, Cheng ;
Liu, Xiqiang ;
Zhou, Xiaofeng .
ORAL ONCOLOGY, 2012, 48 (08) :686-691
[6]   Clusterin silencing in human lung adenocarcinoma cells induces a mesenchymal-to-epithelial transition through modulating the ERK/Slug pathway [J].
Chou, Teh-Ying ;
Chen, Wei-Chieh ;
Lee, An-Chieh ;
Hung, Su-Mei ;
Shih, Neng-Yao ;
Chen, Mei-Yu .
CELLULAR SIGNALLING, 2009, 21 (05) :704-711
[7]   Cutting Edge: MicroRNA-181 Promotes Human NK Cell Development by Regulating Notch Signaling [J].
Cichocki, Frank ;
Felices, Martin ;
McCullar, Valarie ;
Presnell, Steven R. ;
Al-Attar, Ahmad ;
Lutz, Charles T. ;
Miller, Jeffrey S. .
JOURNAL OF IMMUNOLOGY, 2011, 187 (12) :6171-6175
[8]   Function of the zinc-finger transcription factor SNAI2 in cancer and development [J].
Cobaleda, Cesar ;
Perez-Caro, Maria ;
Vicente-Duenas, Carolina ;
Sanchez-Garcia, Isidro .
ANNUAL REVIEW OF GENETICS, 2007, 41 :41-61
[9]   Autoregulation of E-cadherin expression by cadherin-cadherin interactions:: the roles of β-catenin signaling, Slug, and MAPK [J].
Conacci-Sorrell, M ;
Simcha, I ;
Ben-Yedidia, T ;
Blechman, J ;
Savagner, P ;
Ben-Ze'ev, A .
JOURNAL OF CELL BIOLOGY, 2003, 163 (04) :847-857
[10]   TGF-β1 Promotes Migration and Invasion of Salivary Adenoid Cystic Carcinoma [J].
Dong, L. ;
Wang, Y. X. ;
Li, S. L. ;
Yu, G. Y. ;
Gan, Y. H. ;
Li, D. ;
Wang, C. Y. .
JOURNAL OF DENTAL RESEARCH, 2011, 90 (06) :804-809