Knockdown of miR-194-5p inhibits cell proliferation, migration and invasion in breast cancer by regulating the Wnt/β-catenin signaling pathway

被引:38
作者
Yang, Feibiao [1 ]
Xiao, Zhangsheng [1 ]
Zhang, Songze [1 ]
机构
[1] Yinzhou Peoples Hosp Ningbo City, Dept Thyroid & Breast Surg, 251 Baizhang East Rd, Ningbo 315040, Zhejiang, Peoples R China
关键词
breast cancer; SOX17; miR-194-5p; Wnt/beta-catenin; migration; invasion; LUNG-CANCER; STEM-CELLS; SOX17; WNT; MICRORNAS;
D O I
10.3892/ijmm.2018.3897
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Breast cancer is a major public health concern, due to its increasing incidence and limited effective treatment. The present study aimed to investigate the expression of microRNA (miR)-194-5p and its roles in breast cancer. The expression levels of miR-194-5p and SRY-box 17 (SOX17) mRNA were detected in breast cancer tissues and cell lines by reverse transcription-quantitative polymerase chain reaction. The protein expression levels were determined by western blotting. In addition, MTT, colony formation, scratch and Transwell assays were use to evaluate the characteristics of MCF-7 cells with miR-194-5p knockdown. The target verification of miR-194-5p was determined by luciferase reporter assay. Furthermore, tumor-bearing nude mice with miR-194-5p knockdown were used to assess the effects of miR-194-5p on tumor activity. In breast cancer tissues, miR-194-5p was upregulated, whereas SOX17 was downregulated. In addition, the expression levels of SOX17 and phosphorylated (p)-beta-catenin in the cytosol and nucleus were increased in the miR-194-5p inhibitor group. In addition, cell proliferation, migration and invasion were inhibited in response to miR-194-5p knockdown. The luciferase reporter assay confirmed that SOX17 was a target gene of miR-194-5p. In the mouse studies, knockdown of miR-194-5p suppressed tumor growth and promoted SOX17 expression in nude mice with breast cancer. These findings suggested that knockdown of miR-194-5p may increase the expression of SOX17 and regulate the Wnt/beta-catenin signaling pathway in breast cancer cells; therefore, miR-194-5p may be considered a potential target for breast cancer prevention.
引用
收藏
页码:3355 / 3363
页数:9
相关论文
共 34 条
[1]   Promising Druggable Target in Head and Neck Squamous Cell Carcinoma: Wnt Signaling [J].
Aminuddin, Amnani ;
Ng, Pei Yuen .
FRONTIERS IN PHARMACOLOGY, 2016, 7
[2]  
Bodai Balazs I, 2015, Perm J, V19, P48, DOI 10.7812/TPP/14-241
[3]   Overexpression of miR-194 Reverses HMGA2-driven Signatures in Colorectal Cancer [J].
Chang, Hsin-Yi ;
Ye, Shu-Ping ;
Pan, Shiow-Lin ;
Kuo, Tzu-Ting ;
Liu, Bia Chia ;
Chen, Yi-Lin ;
Huang, Tsui-Chin .
THERANOSTICS, 2017, 7 (16) :3889-3900
[4]   miR-194-5p/BCLAF1 deregulation in AML tumorigenesis [J].
Dell'Aversana, C. ;
Giorgio, C. ;
D'Amato, L. ;
Lania, G. ;
Matarese, F. ;
Saeed, S. ;
Di Costanzo, A. ;
Petrizzi, V. Belsito ;
Ingenito, C. ;
Martens, J. H. A. ;
Pallavicini, I. ;
Minucci, S. ;
Carissimo, A. ;
Stunnenberg, H. G. ;
Altucci, L. .
LEUKEMIA, 2017, 31 (11) :2315-2325
[5]   Wnt signaling in triple negative breast cancer is associated with metastasis [J].
Dey, Nandini ;
Barwick, Benjamin G. ;
Moreno, Carlos S. ;
Ordanic-Kodani, Maja ;
Chen, Zhengjia ;
Oprea-Ilies, Gabriella ;
Tang, Weining ;
Catzavelos, Charles ;
Kerstann, Kimberly F. ;
Sledge, George W., Jr. ;
Abramovitz, Mark ;
Bouzyk, Mark ;
De, Pradip ;
Leyland-Jones, Brian R. .
BMC CANCER, 2013, 13
[6]   Sox17 Promoter Methylation in Plasma DNA Is Associated With Poor Survival and Can Be Used as a Prognostic Factor in Breast Cancer [J].
Fu, Deyuan ;
Ren, Chuanli ;
Tan, Haosheng ;
Wei, Jinli ;
Zhu, Yuxiang ;
He, Chunlan ;
Shao, Wenxi ;
Zhang, Jiaxin .
MEDICINE, 2015, 94 (11) :e637
[7]   Wnt/β-catenin signaling pathway inhibits the proliferation and apoptosis of U87 glioma cells via different mechanisms [J].
Gao, Liyang ;
Chen, Bing ;
Li, Jinhong ;
Yang, Fan ;
Cen, Xuecheng ;
Liao, Zhuangbing ;
Long, Xiao'ao .
PLOS ONE, 2017, 12 (08)
[8]   State of the evidence 2017: an update on the connection between breast cancer and the environment [J].
Gray, Janet M. ;
Rasanayagam, Sharima ;
Engel, Connie ;
Rizzo, Jeanne .
ENVIRONMENTAL HEALTH, 2017, 16
[9]  
Greene SB, 2010, CURR DRUG TARGETS, V11, P1059
[10]   Conditional deletion of Sox17 reveals complex effects on uterine adenogenesis and function [J].
Guimaraes-Young, Amy ;
Neff, Traci ;
Dupuy, Adam J. ;
Goodheart, Michael J. .
DEVELOPMENTAL BIOLOGY, 2016, 414 (02) :219-227