miR-223-3p regulates cell growth and apoptosis via FBXW7 suggesting an oncogenic role in human testicular germ cell tumors

被引:42
作者
Liu, Jikai [1 ,2 ]
Shi, Hao [1 ]
Li, Xidan [3 ]
Chen, Gang [2 ]
Larsson, Catharina [1 ]
Lui, Weng-Onn [1 ]
机构
[1] Karolinska Univ Hosp, Dept Oncol Pathol, Karolinska Inst, Canc Ctr Karolinska, SE-17176 Stockholm, Sweden
[2] Fudan Univ, Jinshan Hosp, Dept Urol, Shanghai 201508, Peoples R China
[3] Karolinska Univ Hosp Huddinge, Dept Med Huddinge, SE-14186 Stockholm, Sweden
基金
瑞典研究理事会;
关键词
miR-223-3p; cell growth; apoptosis; FBXW7; TGCT; UBIQUITIN LIGASE FBXW7; HUMAN GASTRIC-CANCER; LYMPHOBLASTIC-LEUKEMIA; SUPPRESSOR; MICRORNA-223; EXPRESSION; PROMOTES; CYCLE; SENSITIVITY; PROGRESSION;
D O I
10.3892/ijo.2016.3807
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
miR-223-3p is deregulated in several tumor types and plays an important role in tumorigenesis and progression. However, its role in the pathogenesis of testicular germ cell tumor (TGCT) remains uncharacterized. We previously demonstrated that miR-223-3p expression was increased in TGCTs compared with normal testes (NT), suggesting that miR-223-3p may have an oncogenic role in TGCT. Using published dataset and The Cancer Genome Atlas database, we validated higher miR-223-3p expression in TGCTs than NT, and found a negative correlation between miR-223-3p and FBXW7 mRNA expression levels. Using both gain- and loss-of-function experiments, we show that miR-223-3p regulates FBXW7 protein expression, cell growth and apoptosis in TGCT cell lines. Additionally, we demonstrate that ectopic expression of the full-length coding sequence of FBXW7 could rescue the cell growth and apoptotic effects mediated by miR-223-3p. Our findings suggest an oncogenic role for miR-223-3p in TGCT, which promotes cell growth and inhibits apoptosis through repression of FBXW7.
引用
收藏
页码:356 / 364
页数:9
相关论文
共 39 条
[21]   Testicular germ cell tumors: biology and clinical update [J].
Mannuel, Heather D. ;
Mitikiri, Nirupama ;
Khan, Maleha ;
Hussain, Arif .
CURRENT OPINION IN ONCOLOGY, 2012, 24 (03) :266-271
[22]   The TAL1 complex targets the FBXW7 tumor suppressor by activating miR-223 in human T cell acute lymphoblastic leukemia [J].
Mansour, Marc R. ;
Sanda, Takaomi ;
Lawton, Lee N. ;
Li, Xiaoyu ;
Kreslavsky, Taras ;
Novina, Carl D. ;
Brand, Marjorie ;
Gutierrez, Alejandro ;
Kelliher, Michelle A. ;
Jamieson, Catriona H. M. ;
von Boehmer, Harald ;
Young, Richard A. ;
Look, A. Thomas .
JOURNAL OF EXPERIMENTAL MEDICINE, 2013, 210 (08) :1545-1557
[23]   Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene [J].
Mao, JH ;
Perez-Iosada, J ;
Wu, D ;
DelRosario, R ;
Tsunematsu, R ;
Nakayama, KI ;
Brown, K ;
Bryson, S ;
Balmain, A .
NATURE, 2004, 432 (7018) :775-779
[24]   A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL) [J].
Mavrakis, Konstantinos J. ;
Van der Meulen, Joni ;
Wolfe, Andrew L. ;
Liu, Xiaoping ;
Mets, Evelien ;
Taghon, Tom ;
Khan, Aly A. ;
Setti, Manu ;
Rondou, Pieter ;
Vandenberghe, Peter ;
Delabesse, Eric ;
Benoit, Yves ;
Socci, Nicholas B. ;
Leslie, Christina S. ;
Van Vlierberghe, Pieter ;
Speleman, Frank ;
Wendel, Hans-Guido .
NATURE GENETICS, 2011, 43 (07) :673-U89
[25]   miR-223 Regulates Cell Growth and Targets Proto-Oncogenes in Mycosis Fungoides/Cutaneous T-Cell Lymphoma [J].
McGirt, Laura Y. ;
Adams, Clare M. ;
Baerenwald, Devin A. ;
Zwerner, Jeffrey P. ;
Zic, John A. ;
Eischen, Christine M. .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2014, 134 (04) :1101-1107
[26]  
McGlynn KA, 2009, FUTURE ONCOL, V5, P1389, DOI [10.2217/fon.09.116, 10.2217/FON.09.116]
[27]  
Mizuno Y, 1993, Nihon Hinyokika Gakkai Zasshi, V84, P1211
[28]   Increasing incidence of testicular cancer in the United States and Europe between 1992 and 2009 [J].
Nigam, Manas ;
Aschebrook-Kilfoy, Briseis ;
Shikanov, Sergey ;
Eggener, Scott .
WORLD JOURNAL OF UROLOGY, 2015, 33 (05) :623-631
[29]  
Ozata DM, CELL DEATH IN PRESS
[30]   Malignant Germ Cell Tumors Display Common MicroRNA Profiles Resulting in Global Changes in Expression of Messenger RNA Targets [J].
Palmer, Roger D. ;
Murray, Matthew J. ;
Saini, Harpreet K. ;
van Dongen, Stijn ;
Abreu-Goodger, Cei ;
Muralidhar, Balaji ;
Pett, Mark R. ;
Thornton, Claire M. ;
Nicholson, James C. ;
Enright, Anton J. ;
Coleman, Nicholas .
CANCER RESEARCH, 2010, 70 (07) :2911-2923