miR-99 inhibits cervical carcinoma cell proliferation by targeting TRIB2

被引:38
作者
Xin, Jia-Xuan [1 ]
Yue, Zhen [1 ]
Zhang, Shuai [2 ]
Jiang, Zhong-Hua [3 ]
Wang, Ping-Yu [1 ,4 ]
Li, You-Jie [1 ]
Pang, Min [1 ]
Xie, Shu-Yang [1 ]
机构
[1] Binzhou Med Univ, Dept Biochem & Mol Biol, Key Lab Tumour Mol Biol Binzhou Med Univ, Yantai 264003, Shandong, Peoples R China
[2] Yantai City Hosp Infect Dis, Yantai 264000, Shandong, Peoples R China
[3] Yantai Tradit Chinese Med Sci TCM, Yantai 264000, Shandong, Peoples R China
[4] Binzhou Med Univ, Dept Epidemiol, Yantai 264003, Shandong, Peoples R China
关键词
microRNAs; cervical carcinoma; gene expression; cell proliferation; miR-99; ACUTE MYELOGENOUS LEUKEMIA; TUMOR SUPPRESSORS; DOWN-REGULATION; C/EBP-ALPHA; CANCER; TRIBBLES; MICRORNAS; GROWTH; FAMILY; MANAGEMENT;
D O I
10.3892/ol.2013.1473
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MicroRNAs (miRNAs) have significant roles in cell processes, including proliferation, apoptosis and stress responses. To investigate the involvement of miR-99 in the inhibition of HeLa cell proliferation, an miR-99 gene expression vector (pU6.1/miR-99), which overexpressed miR-99 in HeLa cells after transient transfection, was constructed. The expression of miR-99 was detected by qPCR. Cell proliferation and apoptosis were analyzed by cell viability, proliferation and apoptosis assays, as well as by electron microscopy. The results showed that overexpression of miR-99 in HeLa cells increased the HeLa cell mortality rate. Moreover, miR-99 overexpression was able to markedly inhibit HeLa cell proliferation according to the 3-(4, 5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide assay. The cell apoptosis rate was significantly higher in pU6.1/miR-99-treated cells compared with that in the control cultures. Increases in intracellular electron density, as well as the proportion of nuclear plasma, blebbing phenomena and apoptotic bodies were observed in pU6.1/miR-99-treated cells compared with control cultures according to electron microscopy analysis. The Tribbles 2 (TRIB2) 3'-untranslated region was also observed to be targeted by miR-99 and the results further demonstrated that miR-99 was able to negatively regulate TRIB2 expression in HeLa cells The results indicate that miR-99 acts as a tumor suppressor gene in HeLa cells, establishing a theoretical basis for its application in cancer therapeutics.
引用
收藏
页码:1025 / 1030
页数:6
相关论文
共 31 条
[1]   MicroRNAs (miRNAs) in cancer invasion and metastasis: therapeutic approaches based on metastasis-related miRNAs [J].
Aigner, Achim .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2011, 89 (05) :445-457
[2]   Induction of cell-specific apoptosis and protection of mice from cancer challenge by a steroid positive compound from Zornia diphylla (L.) Pers [J].
Arunkumar, R. ;
Nair, S. Ajikumaran ;
Subramoniam, A. .
JOURNAL OF PHARMACOLOGY & PHARMACOTHERAPEUTICS, 2012, 3 (03) :233-241
[3]   Down-regulation of the microRNA-99 family members in head and neck squamous cell carcinoma [J].
Chen, Zujian ;
Jin, Yi ;
Yu, Dongsheng ;
Wang, Anxun ;
Mahjabeen, Ishrat ;
Wang, Cheng ;
Liu, Xiqiang ;
Zhou, Xiaofeng .
ORAL ONCOLOGY, 2012, 48 (08) :686-691
[4]   MicroRNAs: Potential biomarkers for cancer diagnosis, prognosis and targets for therapy [J].
Cho, William C. S. .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2010, 42 (08) :1273-1281
[5]   Induction of MET by Ionizing Radiation and Its Role in Radioresistance and Invasive Growth of Cancer [J].
De Bacco, Francesca ;
Luraghi, Paolo ;
Medico, Enzo ;
Reato, Gigliola ;
Girolami, Flavia ;
Perera, Timothy ;
Gabriele, Pietro ;
Comoglio, Paolo M. ;
Boccaccio, Carla .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2011, 103 (08) :645-661
[6]   New surgical approaches for the management of cervical carcinoma [J].
Dursun, P. ;
Ayhan, A. ;
Kuscu, E. .
EJSO, 2008, 34 (05) :487-496
[7]   Tribbles-1 and-2 are tumour suppressors, down-regulated in human acute myeloid leukaemia [J].
Gilby, Daniel C. ;
Sung, Hye Youn ;
Winship, Peter R. ;
Goodeve, Anne C. ;
Reilly, John T. ;
Kiss-Toth, Endre .
IMMUNOLOGY LETTERS, 2010, 130 (1-2) :115-124
[8]   Overexpression of TRIB2 in human lung cancers contributes to tumorigenesis through downregulation of C/EBPα [J].
Grandinetti, K. B. ;
Stevens, T. A. ;
Ha, S. ;
Salamone, R. J. ;
Walker, J. R. ;
Zhang, J. ;
Agarwalla, S. ;
Tenen, D. G. ;
Peters, E. C. ;
Reddy, V. A. .
ONCOGENE, 2011, 30 (30) :3328-3335
[9]   Regulation of Cancer Aggressive Features in Melanoma Cells by MicroRNAs [J].
Greenberg, Eyal ;
Hershkovitz, Liat ;
Itzhaki, Orit ;
Hajdu, Steven ;
Nemlich, Yael ;
Ortenberg, Rona ;
Gefen, Nir ;
Edry, Liat ;
Modai, Shira ;
Keisari, Yona ;
Besser, Michal J. ;
Schachter, Jacob ;
Shomron, Noam ;
Markel, Gal .
PLOS ONE, 2011, 6 (04)
[10]   A genetic link between morphogenesis and cell division during formation of the ventral furrow in Drosophila [J].
Grosshans, J ;
Wieschaus, E .
CELL, 2000, 101 (05) :523-531