miR-516a-3p inhibits breast cancer cell growth and EMT by blocking the Pygo2/Wnt signalling pathway

被引:29
作者
Chi, Yanyan [1 ]
Wang, Feng [1 ]
Zhang, Tengfei [1 ]
Xu, Han [2 ]
Zhang, Yana [1 ]
Shan, Zhengzheng [1 ]
Wu, Shaoxuan [1 ]
Fan, Qingxia [1 ]
Sun, Yan [1 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 1, Dept Oncol, 1 Eastern Jianshe Rd, Zhengzhou 450052, Henan, Peoples R China
[2] Zhengzhou Univ, Affiliated Hosp 1, Dept Breast Dis Surg, Zhengzhou, Henan, Peoples R China
关键词
breast cancer; epithelial-mesenchymal transition; miR-516a-3p; Pygo2; Wnt; EPITHELIAL-MESENCHYMAL TRANSITION; BETA-CATENIN; E-CADHERIN; PROMOTES INVASION; DOWN-REGULATION; LUNG-CANCER; METASTASIS; EXPRESSION; PROLIFERATION; MICRORNAS;
D O I
10.1111/jcmm.14515
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
miR-516a-3p has been reported to play a suppressive role in several types of human tumours. However, the expression level, biological function and fundamental mechanisms of miR-516a-3p in breast cancer remain unclear. In the present study, we found that miR-516a-3p expression was down-regulated and Pygopus2 (Pygo2) expression was up-regulated in human breast cancer tissues and cells. Through analysing the clinicopathological characteristics, we demonstrated that low miR-516a-3p expression or positive Pygo2 expression was a predictor of poor prognosis for patients with breast cancer. The results of a dual luciferase reporter assay and Western blot analysis indicated that Pygo2 was a target gene of miR-516a-3p. Moreover, overexpression of miR-516a-3p inhibited cell growth, migration and invasion as well as epithelial-mesenchymal transition (EMT) of breast cancer cells, whereas reduced miR-516a-3p expression promoted breast cancer cell growth, migration, invasion and EMT. Furthermore, we showed that miR-516a-3p suppressed cell proliferation, metastasis and EMT of breast cancer cells by inhibiting Pygo2 expression. We confirmed that miR-516a-3p exerted an anti-tumour effect by inhibiting the activation of the Wnt/beta-catenin pathway. Finally, xenograft tumour models were used to show that miR-516a-3p inhibited breast cancer cell growth and EMT via suppressing the Pygo2/Wnt signalling pathway. Taken together, these results show that miR-516a-3p inhibits breast cancer cell growth, metastasis and EMT by blocking the Pygo2/Wnt/beta-catenin pathway.
引用
收藏
页码:6295 / 6307
页数:13
相关论文
共 48 条
[1]  
Andrews PGP, 2007, INT J ONCOL, V30, P357
[2]   Breast Cancer-Major Changes in the American Joint Committee on Cancer Eighth Edition Cancer Staging Manual (vol 67, pg 290, 2017) [J].
Giuliano, A. E. ;
Connolly, J. L. ;
Edge, S. B. ;
Mittendorf, E. A. ;
Rugo, H. S. ;
Solin, L. J. ;
Weaver, D. L. ;
Winchester, D. J. ;
Hortobagyi, G. N. .
CA-A CANCER JOURNAL FOR CLINICIANS, 2017, 67 (04) :345-345
[3]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[4]   CYCLIN D1 PROTEIN EXPRESSION AND FUNCTION IN HUMAN BREAST-CANCER [J].
BARTKOVA, J ;
LUKAS, J ;
MULLER, H ;
LUTZHOFT, D ;
STRAUSS, M ;
BARTEK, J .
INTERNATIONAL JOURNAL OF CANCER, 1994, 57 (03) :353-361
[5]  
Belenkaya TY, 2002, DEVELOPMENT, V129, P4089
[6]   MicroRNA-567 dysregulation contributes to carcinogenesis of breast cancer, targeting tumor cell proliferation, and migration [J].
Bertoli, Gloria ;
Cava, Claudia ;
Diceglie, Cecilia ;
Martelli, Cristina ;
Rizzo, Giampiero ;
Piccotti, Francesca ;
Ottobrini, Luisa ;
Castiglioni, Isabella .
BREAST CANCER RESEARCH AND TREATMENT, 2017, 161 (03) :605-616
[7]   Pygo2 Associates with MLL2 Histone Methyltransferase and GCN5 Histone Acetyltransferase Complexes To Augment Wnt Target Gene Expression and Breast Cancer Stem-Like Cell Expansion [J].
Chen, Jiakun ;
Luo, Qicong ;
Yuan, Yuanyang ;
Huang, Xiaoli ;
Cai, Wangyu ;
Li, Chao ;
Wei, Tongzhen ;
Zhang, Ludi ;
Yang, Meng ;
Liu, Qingfeng ;
Ye, Guodong ;
Dai, Xing ;
Li, Boan .
MOLECULAR AND CELLULAR BIOLOGY, 2010, 30 (24) :5621-5635
[8]   Cancer Statistics in China, 2015 [J].
Chen, Wanqing ;
Zheng, Rongshou ;
Baade, Peter D. ;
Zhang, Siwei ;
Zeng, Hongmei ;
Bray, Freddie ;
Jemal, Ahmedin ;
Yu, Xue Qin ;
He, Jie .
CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132
[9]   miR-15 and miR-16 induce apoptosis by targeting BCL2 [J].
Cimmino, A ;
Calin, GA ;
Fabbri, M ;
Iorio, MV ;
Ferracin, M ;
Shimizu, M ;
Wojcik, SE ;
Aqeilan, RI ;
Zupo, S ;
Dono, M ;
Rassenti, L ;
Alder, H ;
Volinia, S ;
Liu, CG ;
Kipps, TJ ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (39) :13944-13949
[10]   Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in Eμ-miR155 transgenic mice [J].
Costinean, S ;
Zanesi, N ;
Pekarsky, Y ;
Tili, E ;
Volinia, S ;
Heerema, N ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (18) :7024-7029