MiR-125b Inhibits Tumor Growth and Promotes Apoptosis of Cervical Cancer Cells by Targeting Phosphoinositide 3-Kinase Catalytic Subunit Delta

被引:83
作者
Cui, Fang [1 ]
Li, Xiuli [1 ,2 ]
Zhu, Xiangyu [1 ]
Huang, Lili [1 ]
Huang, Yongfang [1 ]
Mao, Caiying [1 ]
Yan, Qi [1 ]
Zhu, Jianhong [1 ]
Zhao, Wenxia [1 ]
Shi, Hong [1 ]
机构
[1] Shanghai Jiangwan Hosp, Dept Gynaecol & Obstet Med, Shanghai 200434, Peoples R China
[2] Tongji Univ, Dept Dermatol, Sch Med, Shanghai Peoples Hosp 10, Shanghai 200092, Peoples R China
关键词
Phosphoinositide 3-kinase catalytic subunit delta; Post-transcriptional regulation; Cervical cancer; HeLa; Apoptosis; EXPRESSION; MICRORNAS; CARCINOMA; PROLIFERATION; GENES;
D O I
10.1159/000343320
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Backgroud: microRNAs (miRNAs) are involved in cancer-related processes. The miRNA-125b (miR-125b) has been identified as miRNA over-expressed in a wide variety of cancers. However, the role of miR-125b in the context of cervical carcinoma remains unknown. Methods: In this study, the effect of miR-125b on the proliferation and apoptosis of human cervical cells was analyzed by MTT assay and Flow cytometry analysis. we identified phosphoinositide 3-kinase catalytic subunit delta (PIK3CD) as a novel miR-125b target. Results: overexpression of miR-125b in HeLa cervical cancer cells decreased cell proliferation, induced apoptosis and downregulated expression of PIK3CD. To identify the mechanisms responsible, we investigated the PI3K/Akt pathway and found that PI3K, phospho-Akt, and phospho-mTOR were all downregulated, while Bid was up-regulated in miR-125b-overexpressing subclones. In vivo, over expression of miR-125b in HeLa cells markedly reduced their ability to form tumors. Conclusion: these results suggest that miR-125b suppresses tumor growth activity by targeting the PI3K/Akt/mTOR signal-ing pathway, and may provide a target for effective therapies. Copyright (C) 2012 S. Karger AG, Basel
引用
收藏
页码:1310 / 1318
页数:9
相关论文
共 32 条
[1]
Regulation of placenta growth factor by microRNA-125b in hepatocellular cancer [J].
Alpini, Gianfranco ;
Glaser, Shannon S. ;
Zhang, Jing-Ping ;
Francis, Heather ;
Han, Yuyan ;
Gong, Jiao ;
Stokes, Allison ;
Francis, Taylor ;
Hughart, Nathan ;
Hubble, Levi ;
Zhuang, Shi-Mei ;
Meng, Fanyin .
JOURNAL OF HEPATOLOGY, 2011, 55 (06) :1339-1345
[2]
The functions of animal microRNAs [J].
Ambros, V .
NATURE, 2004, 431 (7006) :350-355
[3]
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
[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]
MicroRNA signatures in human cancers [J].
Calin, George A. ;
Croce, Carlo M. .
NATURE REVIEWS CANCER, 2006, 6 (11) :857-866
[6]
Hu X, 2011, CANCER RES, V70, P1441
[7]
miRNA profiling for diagnosis and prognosis of human cancer [J].
Jay, Chris ;
Nemunaitis, John ;
Chen, Patrick ;
Fulgham, Pat ;
Tong, Alex W. .
DNA AND CELL BIOLOGY, 2007, 26 (05) :293-300
[8]
The let-7 MicroRNA represses cell proliferation pathways in human cells [J].
Johnson, Charles D. ;
Esquela-Kerscher, Aurora ;
Stefani, Giovanni ;
Byrom, Nlike ;
Kelnar, Kevin ;
Ovcharenko, Dmitriy ;
Wilson, Mike ;
Wang, Xiaowei ;
Shelton, Jeffrey ;
Shingara, Jaclyn ;
Chin, Lena ;
Brown, David ;
Slack, Frank J. .
CANCER RESEARCH, 2007, 67 (16) :7713-7722
[9]
Expression of Bax, p53, and p27/kip in patients with papillary thyroid carcinoma with or without cervical nodal metastasis [J].
Karlidag, Turgut ;
Cobanoglu, Bengu ;
Keles, Erol ;
Alpay, Hayrettin Cengiz ;
Ozercan, Ibrahim ;
Kaygusuz, Irfan ;
Yalcin, Sinasi ;
Sakallioglu, Oner .
AMERICAN JOURNAL OF OTOLARYNGOLOGY, 2007, 28 (01) :31-36
[10]
A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes [J].
Kent, O. A. ;
Mendell, J. T. .
ONCOGENE, 2006, 25 (46) :6188-6196