miR-200 affects tamoxifen resistance in breast cancer cells through regulation of MYB

被引:51
作者
Gao, Yu [1 ]
Zhang, Wenzhi [2 ]
Liu, Chengwen [3 ]
Li, Guanghua [4 ]
机构
[1] Tianjin First Cent Hosp, Dept Gen Surg, 24 Fukang Rd, Tianjin 300204, Peoples R China
[2] Innosci Res Sdn Bhd, Suites B-5-7,Level 5,Sky Pk One City, Subang Jaya 47650, Selangor, Malaysia
[3] Matern & Child Hlth Care Zaozhuang, Dept Obstet & Gynecol, Zaozhuang 277100, Shandong, Peoples R China
[4] Shandong Univ, Hosp 2, Dept Gen Surg, 247 Beiyuan Rd, Jinan 250033, Shandong, Peoples R China
关键词
EPITHELIAL-MESENCHYMAL TRANSITION; C-MYB; DOWN-REGULATION; EXPRESSION; FAMILY; CONTRIBUTES; PACLITAXEL; MICRORNAS;
D O I
10.1038/s41598-019-54289-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Resistance to tamoxifen is a major clinical challenge. Research in recent years has identified epigenetic changes as mediated by dysregulated miRNAs that can possibly play a role in resistance to tamoxifen in breast cancer patients expressing estrogen receptor (ER). We report here elevated levels of EMT markers (vimentin and ZEB1/2) and reduced levels of EMT-regulating miR-200 (miR-200b and miR-200c) in ER-positive breast cancer cells, MCF-7, that were resistant to tamoxifen, in contrast with the naive parental MCF-7 cells that were sensitive to tamoxifen. Further, we established regulation of c-MYB by miR-200 in our experimental model. C-MYB was up-regulated in tamoxifen resistant cells and its silencing significantly decreased resistance to tamoxifen and the EMT markers. Forced over-expression of miR-200b/c reduced c-MYB whereas reduced expression of miR-200b/c resulted in increased c-MYB We further confirmed the results in other ER-positive breast cancer cells T47D cells where forced overexpression of c-MYB resulted in induction of EMT and significantly increased resistance to tamoxifen. Thus, we identify a novel mechanism of tamoxifen resistance in breast tumor microenvironment that involves miR-200-MYB signaling.
引用
收藏
页数:6
相关论文
共 50 条
[41]   The prognostic value of the miR-200 family in ovarian cancer: a meta-analysis [J].
Shi, Can ;
Zhang, Zhenyu .
ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA, 2016, 95 (05) :505-512
[42]   miRNAs as emerging predictors of tamoxifen resistance in breast cancer [J].
Beilankouhi, Elmira Aboutalebi Vand ;
Safaralizadeh, Reza ;
Nejati, Babak ;
Sanaat, Zohreh ;
Gharamaleki, Jalil Vaez ;
Esfahani, Ali ;
Gholami, Nasrin ;
Sarbakhsh, Parvin ;
Mohammadian, Jamal ;
Mehdizadeh, Amir .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2025,
[43]   The role of MYB proto-oncogene like 2 in tamoxifen resistance in breast cancer [J].
Li, Xia ;
Zhang, Xi ;
Wu, Cong-Cong ;
Li, Ping-Ping ;
Fu, Yi-Mou ;
Xie, Li-Hua ;
Sun, Shuang-Shuang ;
Zhou, Ying-Ying ;
Zhu, Bao-Ling .
JOURNAL OF MOLECULAR HISTOLOGY, 2021, 52 (01) :21-30
[44]   Downregulation of miR-200c-3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2 [J].
Chen, Junqing ;
Tian, Wei ;
He, Haifei ;
Chen, Feng ;
Huang, Jian ;
Wang, Xiaojia ;
Chen, Zhanhong .
ONCOLOGY REPORTS, 2018, 40 (06) :3821-3829
[45]   Identification of an Enhancer That Increases miR-200b∼200a∼429 Gene Expression in Breast Cancer Cells [J].
Attema, Joanne L. ;
Bert, Andrew G. ;
Lim, Yat-Yuen ;
Kolesnikoff, Natasha ;
Lawrence, David M. ;
Pillman, Katherine A. ;
Smith, Eric ;
Drew, Paul A. ;
Khew-Goodall, Yeesim ;
Shannon, Frances ;
Goodall, Gregory J. .
PLOS ONE, 2013, 8 (09)
[46]   miR-200 family promotes podocyte differentiation through repression of RSAD2 [J].
Li, Zhigui ;
Yin, Hongqiang ;
Hao, Shuang ;
Wang, Lifeng ;
Gao, Jing ;
Tan, Xiaoyue ;
Yang, Zhuo .
SCIENTIFIC REPORTS, 2016, 6
[47]   Loss of miR-200 Inhibition of Suz12 Leads to Polycomb-Mediated Repression Required for the Formation and Maintenance of Cancer Stem Cells [J].
Iliopoulos, Dimitrios ;
Lindahl-Allen, Marianne ;
Polytarchou, Christos ;
Hirsch, Heather A. ;
Tsichlis, Philip N. ;
Struhl, Kevin .
MOLECULAR CELL, 2010, 39 (05) :761-772
[48]   Let-7 and miR-200 microRNAs Guardians against pluripotency and cancer progression [J].
Peter, Marcus E. .
CELL CYCLE, 2009, 8 (06) :843-852
[49]   LncRNA SNHG6 sponges miR-101 and induces tamoxifen resistance in breast cancer cells through induction of EMT [J].
Khan, Mohammad Imran ;
Ahmad, Aamir .
FRONTIERS IN ONCOLOGY, 2022, 12
[50]   Diagnostic and prognostic value of miR-200 family in breast cancer: A meta-analysis and systematic review [J].
Thuy Thi Chung Duong ;
Thu Huynh Ngoc Nguyen ;
Thanh Thi Ngoc Nguyen ;
Luan Huu Huynh ;
Hoang Phan Ngo ;
Hue Thi Nguyen .
CANCER EPIDEMIOLOGY, 2022, 77