MicroRNA-21 promotes the ovarian teratocarcinoma PA1 cell line by sustaining cancer stem/progenitor populations in vitro

被引:33
作者
Chung, Wei-Min [1 ,2 ]
Chang, Wei-Chun [2 ]
Chen, Lumin [2 ,3 ]
Chang, Ying-Yi [2 ]
Shyr, Chih-Rong [2 ,4 ]
Hung, Yao-Ching [1 ,2 ]
Ma, Wen-Lung [1 ,2 ]
机构
[1] China Med Univ, Sch Med, Grad Inst Clin Med Sci, Taichung 404, Taiwan
[2] China Med Univ Hosp, Sex Hormone Res Ctr, Dept OBS & GYN, Taichung 404, Taiwan
[3] BenQ Med Ctr, Dept OBS & GYN, Suzhou 215000, Zhejiang, Peoples R China
[4] China Med Univ, Dept Med Technol, Taichung 404, Taiwan
关键词
microRNA; 21; Ovarian teratocarcinoma; Cancer stem/progenitor cells; CD133; MESSENGER-RNA DEGRADATION; STEM-CELLS; MIGRATION ABILITIES; CD133; EXPRESSION; SIDE POPULATION; MIR-21; INVASION; PROLIFERATION; SENSITIVITY; CISPLATIN;
D O I
10.1186/scrt247
中图分类号
Q813 [细胞工程];
学科分类号
100113 [医学细胞生物学];
摘要
Introduction: Resistance of cancer stem/progenitor cells (CSPCs) to chemotherapy can lead to cancer relapse. Ovarian teratocarcinoma (OVTC) arises from germ cells and comprises pluripotent cells that can be used to study cancer cell stemness. In this study, we evaluated whether microRNA-21 (miR-21) promotes ovarian teratocarcinoma by maintaining cancer stem/progenitor populations. Methods: The lentiviral delivery system was used to upregulate or to suppress the expression of miR-21 in the human ovarian teratocarcinoma cell line PA1 and cell growth assays were used to monitor the expression of miR-21 at different time points. Antibodies directed toward CD133, a stem cell marker, were used to identify CSPCs in the PA1 cell population, and the level of miR-21 expression was determined in enriched CSPCs. Stem cell functional assays (sphere assay and assays for CD133 expression) were used to assess the effects of miR-21 on progression of the CD133+ population. Results: Knockdown of miR-21 in PA1 cells attenuated growth of PA1 cells whereas overexpression of miR-21 promoted cell growth. Moreover, knockdown of miR-21 resulted in a marked reduction in the CD133+ population and sphere formation of CSPCs. In contrast, overexpression of miR-21 resulted in a marked increase in the population of CD133+ cells as well as sphere formation of CSPCs. Conclusions: MicroRNA-21 plays a significant role in cancer growth by regulating stemness in cancer cells.
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页数:10
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共 56 条
[1]
Epigenetic regulation of CD133 and tumorigenicity of CD133+ovarian cancer cells [J].
Baba, T. ;
Convery, P. A. ;
Matsumura, N. ;
Whitaker, R. S. ;
Kondoh, E. ;
Perry, T. ;
Huang, Z. ;
Bentley, R. C. ;
Mori, S. ;
Fujii, S. ;
Marks, J. R. ;
Berchuck, A. ;
Murphy, S. K. .
ONCOGENE, 2009, 28 (02) :209-218
[2]
MicroRNA-21 regulates the sensitivity of diffuse large B-cell lymphoma cells to the CHOP chemotherapy regimen [J].
Bai, Haitao ;
Wei, Ju ;
Deng, Chong ;
Yang, Xiaoyu ;
Wang, Chun ;
Xu, Rang .
INTERNATIONAL JOURNAL OF HEMATOLOGY, 2013, 97 (02) :223-231
[3]
Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer [J].
Bapat, SA ;
Mali, AM ;
Koppikar, CB ;
Kurrey, NK .
CANCER RESEARCH, 2005, 65 (08) :3025-3029
[4]
Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment [J].
Bertolini, Giulia ;
Roz, Luca ;
Perego, Paola ;
Tortoreto, Monica ;
Fontanella, Enrico ;
Gatti, Laura ;
Pratesi, Graziella ;
Fabbri, Alessandra ;
Andriani, Francesca ;
Tinelli, Stella ;
Roz, Elena ;
Caserini, Roberto ;
Lo Vullo, Salvatore ;
Camerini, Tiziana ;
Mariani, Luigi ;
Delia, Domenico ;
Calabro, Elisa ;
Pastorino, Ugo ;
Sozzi, Gabriella .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (38) :16281-16286
[5]
Gefitinib resistance in HCC mahlavu cells: Upregulation of CD133 expression, activation of IGF-1R signaling pathway, and enhancement of IGF-1R nuclear translocation [J].
Bodzin, Adam S. ;
Wei, Zhengyu ;
Hurtt, Reginald ;
Gu, Tina ;
Doria, Cataldo .
JOURNAL OF CELLULAR PHYSIOLOGY, 2012, 227 (07) :2947-2952
[6]
Disaggregation and invasion of ovarian carcinoma ascites spheroids [J].
Burleson, KM ;
Boente, MP ;
Pambuccian, SE ;
Skubitz, APN .
JOURNAL OF TRANSLATIONAL MEDICINE, 2006, 4 (1)
[7]
Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells [J].
Chekulaeva, Marina ;
Filipowicz, Witold .
CURRENT OPINION IN CELL BIOLOGY, 2009, 21 (03) :452-460
[8]
Micro-RNA-21 regulates the sensitivity to cisplatin in human neuroblastoma cells [J].
Chen, Yun ;
Tsai, Ya-Hui ;
Fang, Yu ;
Tseng, Sheng-Hong .
JOURNAL OF PEDIATRIC SURGERY, 2012, 47 (10) :1797-1805
[9]
CD133 Expression Defines a Tumor Initiating Cell Population in Primary Human Ovarian Cancer [J].
Curley, Michael D. ;
Therrien, Vanessa A. ;
Cummings, Christine L. ;
Sergent, Petra A. ;
Koulouris, Carolyn R. ;
Friel, Anne M. ;
Roberts, Drucilla J. ;
Seiden, Michael V. ;
Scadden, David T. ;
Rueda, Bo R. ;
Foster, Rosemary .
STEM CELLS, 2009, 27 (12) :2875-2883
[10]
Targeting of the Tumor Suppressor GRHL3 by a miR-21-Dependent Proto-Oncogenic Network Results in PTEN Loss and Tumorigenesis [J].
Darido, Charbel ;
Georgy, Smitha R. ;
Wilanowski, Tomasz ;
Dworkin, Sebastian ;
Auden, Alana ;
Zhao, Quan ;
Rank, Gerhard ;
Srivastava, Seema ;
Finlay, Moira J. ;
Papenfuss, Anthony T. ;
Pandolfi, Pier Paolo ;
Pearson, Richard B. ;
Jane, Stephen M. .
CANCER CELL, 2011, 20 (05) :635-648