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
[11]   miR-145 inhibits tumor growth and metastasis by targeting metadherin in high-grade serous ovarian carcinoma [J].
Dong, Ruifen ;
Liu, Xiaolin ;
Zhang, Qing ;
Jiang, Zhijun ;
Li, Yingwei ;
Wei, Yuyan ;
Li, Yinuo ;
Yang, Qifeng ;
Liu, Jinsong ;
Wei, Jian-Jun ;
Shao, Changshun ;
Liu, Zhaojian ;
Kong, Beihua .
ONCOTARGET, 2014, 5 (21) :10816-10829
[12]   Oncomirs - microRNAs with a role in cancer [J].
Esquela-Kerscher, A ;
Slack, FJ .
NATURE REVIEWS CANCER, 2006, 6 (04) :259-269
[13]   β-catenin as a potential key target for tumor suppression [J].
Fu, Yuejun ;
Zheng, Shuhua ;
An, Na ;
Athanasopoulos, Takis ;
Popplewell, Linda ;
Liang, Aihua ;
Li, Ke ;
Hu, Changchen ;
Zhu, Yajing .
INTERNATIONAL JOURNAL OF CANCER, 2011, 129 (07) :1541-1551
[14]   The mir-200 family and mir-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1 [J].
Gregory, Philip A. ;
Bert, Andrew G. ;
Paterson, Emily L. ;
Barry, Simon C. ;
Tsykin, Anna ;
Farshid, Gelareh ;
Vadas, Mathew A. ;
Khew-Goodall, Yeesim ;
Goodall, Gregory J. .
NATURE CELL BIOLOGY, 2008, 10 (05) :593-601
[15]  
HAN X, 2014, CANCER GENE THER, V21, P60, DOI DOI 10.1038/CGT.2013.82
[16]   MicroRNA miR-335 is crucial for the BRCA1 regulatory cascade in breast cancer development [J].
Heyn, Holger ;
Engelmann, Maria ;
Schreek, Sabine ;
Ahrens, Philipp ;
Lehmann, Ulrich ;
Kreipe, Hans ;
Schlegelberger, Brigitte ;
Beger, Carmela .
INTERNATIONAL JOURNAL OF CANCER, 2011, 129 (12) :2797-2806
[17]   PTBP3-Mediated Regulation of ZEB1 mRNA Stability Promotes Epithelial-Mesenchymal Transition in Breast Cancer [J].
Hou, Pingfu ;
Li, Lin ;
Chen, Fang ;
Chen, Yansu ;
Liu, Hui ;
Li, Jingjing ;
Bai, Jin ;
Zheng, Junnian .
CANCER RESEARCH, 2018, 78 (02) :387-398
[18]   PTK6 Inhibition Suppresses Metastases of Triple-Negative Breast Cancer via SNAIL-Dependent E-Cadherin Regulation [J].
Ito, Koichi ;
Park, Sun Hee ;
Nayak, Anupma ;
Byerly, Jessica H. ;
Irie, Hanna Y. .
CANCER RESEARCH, 2016, 76 (15) :4406-4417
[19]   β-catenin, a novel prognostic marker for breast cancer:: Its roles in cyclin D1 expression and cancer progression [J].
Lin, SY ;
Xia, WY ;
Wang, JC ;
Kwong, KY ;
Spohn, B ;
Wen, Y ;
Pestell, RG ;
Hung, MC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (08) :4262-4266
[20]   An In Vivo Screen Identifies PYGO2 as a Driver for Metastatic Prostate Cancer [J].
Lu, Xin ;
Pan, Xiaolu ;
Wu, Chang-Jiun ;
Zhao, Di ;
Feng, Shan ;
Zang, Yong ;
Lee, Rumi ;
Khadka, Sunada ;
Amin, Samirkumar B. ;
Jin, Eun-Jung ;
Shang, Xiaoying ;
Deng, Pingna ;
Luo, Yanting ;
Morgenlander, William R. ;
Weinrich, Jacqueline ;
Lu, Xuemin ;
Jiang, Shan ;
Chang, Qing ;
Navone, Nora M. ;
Troncoso, Patricia ;
DePinho, Ronald A. ;
Wang, Y. Alan .
CANCER RESEARCH, 2018, 78 (14) :3823-3833