MicroRNA-200b Is Overexpressed in Endometrial Adenocarcinomas and Enhances MMP2 Activity by Downregulating TIMP2 in Human Endometrial Cancer Cell Line HEC-1A Cells

被引:43
作者
Dai, Yinmei [1 ]
Xia, Wei [2 ]
Song, Tao [3 ]
Su, Xueting [2 ]
Li, Jie [2 ]
Li, Shaohua [2 ]
Chen, Ying [2 ]
Wang, Wei [2 ]
Ding, Hongmei [2 ]
Liu, Xuemei [2 ]
Li, Hui [2 ]
Zhao, Qiang [2 ]
Shao, Ningsheng [2 ]
机构
[1] Capital Med Univ, Beijing Obstet & Gynecol Hosp, Beijing, Peoples R China
[2] Beijing Inst Basic Med Sci, Beijing 100850, Peoples R China
[3] Chinese Peoples Liberat Army Gen Hosp, Beijing, Peoples R China
关键词
GASTRIC-CANCER; MIR-200; FAMILY; NUCLEAR EXPORT; EXPRESSION; PROLIFERATION; CARCINOMA; INVASION; GENES; AND-9; ZEB1;
D O I
10.1089/nat.2012.0385
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
MicroRNAs (miRNAs) play important roles in tumorigenesis and metastasis. In this study, we investigated miR-200b expression in endometrial adenocarcinomas and normal adjacent tissues and found that miR-200b is more highly expressed in cancer tissues than in normal adjacent tissues. A novel target of miR-200b, tissue inhibitor of metalloproteinase 2 (TIMP2), was predicted using a bioinformatics approach and was confirmed in human endometrial cancer cell line HEC-1A cells by luciferase assay, quantitative real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. We found that miR-200b repressed TIMP2 expression at both the messenger RNA and protein levels, although a family member, miR-200a, had no such effect. Using reverse gelatin zymography, we showed that miR-200b enhances matrix metallopeptidase 2 (MMP2) activity by downregulating TIMP2 expression in HEC-1A cells. These data suggest that miR-200b may play an important role in the metastasis of endometrial adenocarcinomas.
引用
收藏
页码:29 / 34
页数:6
相关论文
共 33 条
[1]   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
[2]   MicroRNAs and their target messenger RNAs associated with endometrial carcinogenesis [J].
Boren, Todd ;
Xiong, Yin ;
Hakam, Ardeshir ;
Wenham, Robert ;
Apte, Sachin ;
Wei, ZhengZheng ;
Kamath, Siddharth ;
Chen, Dung-Tsa ;
Dressman, Holly ;
Lancaster, Johnathan M. .
GYNECOLOGIC ONCOLOGY, 2008, 110 (02) :206-215
[3]   Menstrual activity of matrix metalloproteinases is decreased in endometrium regenerating after thermal ablation [J].
Brun, J. L. ;
Galant, C. ;
Delvaux, D. ;
Lemoine, P. ;
Henriet, P. ;
Courtoy, P. J. ;
Marbaix, E. .
HUMAN REPRODUCTION, 2009, 24 (02) :333-340
[4]   Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers [J].
Calin, GA ;
Sevignani, C ;
Dan Dumitru, C ;
Hyslop, T ;
Noch, E ;
Yendamuri, S ;
Shimizu, M ;
Rattan, S ;
Bullrich, F ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (09) :2999-3004
[5]   Increased expression of miR-148b in ovarian carcinoma and its clinical significance [J].
Chang, Hua ;
Zhou, Xin ;
Wang, Zhen-Ning ;
Song, Yong-Xi ;
Zhao, Fang ;
Gao, Peng ;
Chiang, Yeunpo ;
Xu, Hui-Mian .
MOLECULAR MEDICINE REPORTS, 2012, 5 (05) :1277-1280
[6]  
Chau KY, 2008, EYE, V22, P855, DOI [10.1038/sj.eye.6702722x, 10.1038/sj.eye.6702722]
[7]   Intronic miR-26b controls neuronal differentiation by repressing its host transcript, ctdsp2 [J].
Dill, Holger ;
Linder, Bastian ;
Fehr, Alexander ;
Fischer, Utz .
GENES & DEVELOPMENT, 2012, 26 (01) :25-30
[8]   Down-regulation of miR-141 in gastric cancer and its involvement in cell growth [J].
Du, Ying ;
Xu, Yanjun ;
Ding, Ling ;
Yao, Haomi ;
Yu, Hong ;
Zhou, Tianhua ;
Si, Jianmin .
JOURNAL OF GASTROENTEROLOGY, 2009, 44 (06) :556-561
[9]   MicroRNA-20a inhibits stress-induced cardiomyocyte apoptosis involving its novel target Egln3/PHD3 [J].
Frank, Derk ;
Gantenberg, Johanne ;
Boomgaarden, Inka ;
Kuhn, Christian ;
Will, Rainer ;
Jarr, Kai-Uwe ;
Eden, Matthias ;
Kramer, Kristin ;
Luedde, Mark ;
Mairbaeurl, Heimo ;
Katus, Hugo A. ;
Frey, Norbert .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2012, 52 (03) :711-717
[10]   A novel method to monitor the expression of microRNAs [J].
Fu, HJ ;
Zhu, L ;
Yang, M ;
Zhang, ZY ;
Tie, Y ;
Jiang, H ;
Sun, ZX ;
Zheng, XF .
MOLECULAR BIOTECHNOLOGY, 2006, 32 (03) :197-204