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
[21]   MicroRNA genes are transcribed by RNA polymerase II [J].
Lee, Y ;
Kim, M ;
Han, JJ ;
Yeom, KH ;
Lee, S ;
Baek, SH ;
Kim, VN .
EMBO JOURNAL, 2004, 23 (20) :4051-4060
[22]   miRNA-223 Promotes Gastric Cancer Invasion and Metastasis by Targeting Tumor Suppressor EPB41L3 [J].
Li, Xiaohua ;
Zhang, Ying ;
Zhang, Hongwei ;
Liu, Xiaonan ;
Gong, Taiqian ;
Li, Mengbin ;
Sun, Li ;
Ji, Gang ;
Shi, Yongquan ;
Han, Zheyi ;
Han, Shuang ;
Nie, Yongzhang ;
Chen, Xiong ;
Zhao, Qinchuan ;
Ding, Jie ;
Wu, Kaichun ;
Daiming, Fan .
MOLECULAR CANCER RESEARCH, 2011, 9 (07) :824-833
[23]   Exploiting salivary miR-31 as a clinical biomarker of oral squamous cell carcinoma [J].
Liu, Chung-Ji ;
Lin, Shu-Chun ;
Yang, Cheng-Chieh ;
Cheng, Hui-Wen ;
Chang, Kuo-Wei .
HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, 2012, 34 (02) :219-224
[24]  
Liu Xia, 2009, Zhonghua Yi Xue Za Zhi, V89, P1365
[25]   Nuclear export of microRNA precursors [J].
Lund, E ;
Güttinger, S ;
Calado, A ;
Dahlberg, JE ;
Kutay, U .
SCIENCE, 2004, 303 (5654) :95-98
[26]   MicroRNA expression profiles in serous ovarian carcinoma [J].
Nam, Eun Ji ;
Yoon, Heejei ;
Kim, Sang Wun ;
Kim, Hoguen ;
Kim, Young Tae ;
Kim, Jae Hoon ;
Kim, Jae Wook ;
Kim, Sunghoon .
CLINICAL CANCER RESEARCH, 2008, 14 (09) :2690-2695
[27]   The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2 [J].
Park, Sun-Mi ;
Gaur, Arti B. ;
Lengyel, Ernst ;
Peter, Marcus E. .
GENES & DEVELOPMENT, 2008, 22 (07) :894-907
[28]   The Impact of Eliminating Socioeconomic and Racial Disparities on Premature Cancer Deaths [J].
Siegel, Rebecca ;
Ward, Elizabeth ;
Brawley, Otis ;
Jemal, Ahmedin .
CA-A CANCER JOURNAL FOR CLINICIANS, 2011, 61 (04) :212-236
[29]   The miR200 Family of MicroRNAs Regulates WAVE3-dependent Cancer Cell Invasion [J].
Sossey-Alaoui, Khalid ;
Bialkowska, Katarzyna ;
Plow, Edward F. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (48) :33019-33029
[30]   miR-152 Is a Tumor Suppressor microRNA That Is Silenced by DNA Hypermethylation in Endometrial Cancer [J].
Tsuruta, Tomohiko ;
Kozaki, Ken-ichi ;
Uesugi, Atsushi ;
Furuta, Mayuko ;
Hirasawa, Akira ;
Imoto, Issei ;
Susumu, Nobuyuki ;
Aoki, Daisuke ;
Inazawa, Johji .
CANCER RESEARCH, 2011, 71 (20) :6450-6462