MicroRNA-375 targets Hippo-signaling effector YAP in liver cancer and inhibits tumor properties

被引:258
作者
Liu, Angela M. [1 ,2 ,3 ]
Poon, Ronnie T. P. [3 ]
Luk, John M. [1 ,2 ,3 ]
机构
[1] Natl Univ Singapore, Dept Pharmacol, Singapore 117597, Singapore
[2] Natl Univ Singapore, Dept Surg, Singapore 117597, Singapore
[3] Univ Hong Kong, Dept Surg, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China
关键词
MicroRNA; Hepatocellular carcinoma; Hippo signaling; YAP; Carcinogenesis; HEPATOCELLULAR-CARCINOMA; SUPPRESSOR GENE; SIZE-CONTROL; EXPRESSION; GROWTH; METASTASIS; SIGNATURE; ONCOGENE; MAMMALS; PATHWAY;
D O I
10.1016/j.bbrc.2010.03.036
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
Hepatocellular carcinoma (HCC) is a malignant form of liver cancer that ranks the second leading cause of cancer-related deaths in China and many Asia regions The dismal outcome reflects the need for a better understanding of the transcriptional control of oncogenic signaling pathway. Our recent findings have identified yes-associated protein (YAP) is a potent oncogenic driver and independent prognostic risk factor of HCC The present study aims to elucidate the transcriptional regulation of YAP targeted by microRNA (miRNA) miR-375 is a putative target and was found significantly down-regulated in the tumor versus adjacent non-tumor tissues of HCC patients (n = 48) As determined by luciferase reporter assay, we found ectopic expression of miR-375 could diminish the transcriptional activity of YAP Furthermore, immunoblotting revealed miR-375 suppressed endogenous YAP protein level Functional assays showed that miR-375 was able to inhibit proliferation and invasion of HCC cells Conclusion miR-375 is an important regulator of YAP oncogene. implicating a potential therapeutic role in HCC treatment (C) 2010 Elsevier Inc All rights reserved.
引用
收藏
页码:623 / 627
页数:5
相关论文
共 21 条
[1]   Elucidation of a universal size-control mechanism in Drosophila and mammals [J].
Dong, Jixin ;
Feldmann, Georg ;
Huang, Jianbin ;
Wu, Shian ;
Zhang, Nailing ;
Comerford, Sarah A. ;
Gayyed, Mariana F. ;
Anders, Robert A. ;
Maitra, Anirban ;
Pan, Duojia .
CELL, 2007, 130 (06) :1120-1133
[2]   miR-375 targets 3'-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic β-cells [J].
El Ouaamari, Abdelfattah ;
Baroukh, Nadine ;
Martens, Geert A. ;
Lebrun, Patricia ;
Pipeleers, Daniel ;
van Obberghen, Emmanuel .
DIABETES, 2008, 57 (10) :2708-2717
[3]   Predicting prognosis in hepatocellular carcinoma after curative surgery with common clinicopathologic parameters [J].
Hao, Ke ;
Luk, John M. ;
Lee, Nikki P. Y. ;
Mao, Mao ;
Zhang, Chunsheng ;
Ferguson, Mark D. ;
Lamb, John ;
Dai, Hongyue ;
Ng, Irene O. ;
Sham, Pak C. ;
Poon, Ronnie T. P. .
BMC CANCER, 2009, 9
[4]  
Johnson SM, 2005, CELL, V120, P635, DOI 10.1016/j.cell.2005.01.014
[5]   MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations [J].
Ladeiro, Yannick ;
Couchy, Gabrielle ;
Balabaud, Charles ;
Bioulac-Sage, Paulette ;
Pelletier, Laura ;
Rebouissou, Sandra ;
Zucman-Rossi, Jessica .
HEPATOLOGY, 2008, 47 (06) :1955-1963
[6]   Expression profiling identifies microRNA signature in pancreatic cancer [J].
Lee, Eun Jon ;
Gusev, Yuriy ;
Jiang, Jinmai ;
Nuovo, Gerard J. ;
Lerner, Megan R. ;
Frankel, Wendy L. ;
Morgan, Daniel L. ;
Postier, Russell G. ;
Brackett, Daniel J. ;
Schmittgen, Thomas D. .
INTERNATIONAL JOURNAL OF CANCER, 2007, 120 (05) :1046-1054
[7]   Proteomic Expression Signature Distinguishes Cancerous and Nonmalignant Tissues in Hepatocellular Carcinoma [J].
Lee, Nikki P. ;
Chen, Lei ;
Lin, Marie C. ;
Tsang, Felice H. ;
Yeung, Chun ;
Poon, Ronnie T. ;
Peng, Jirun ;
Leng, Xisheng ;
Beretta, Laura ;
Sun, Stella ;
Day, Philip J. ;
Luk, John M. .
JOURNAL OF PROTEOME RESEARCH, 2009, 8 (03) :1293-1303
[8]   The tumor suppressor microRNA let-7 represses the HMGA2 oncogene [J].
Lee, Yong Sun ;
Dutta, Anindya .
GENES & DEVELOPMENT, 2007, 21 (09) :1025-1030
[9]   Targeting Cadherin-17 Inactivates Wnt Signaling and Inhibits Tumor Growth in Liver Carcinoma [J].
Liu, Ling Xiao ;
Lee, Nikki P. ;
Chan, Vivian W. ;
Xue, Wen ;
Zender, Lars ;
Zhang, Chunsheng ;
Mao, Mao ;
Dai, Hongyue ;
Wang, Xiao Lin ;
Xu, Michelle Z. ;
Lee, Terence K. ;
Ng, Irene O. ;
Chen, Yangchao ;
Kung, Hsiang-fu ;
Lowe, Scott W. ;
Poon, Ronnie T. P. ;
Wang, Jian Hua ;
Luk, John M. .
HEPATOLOGY, 2009, 50 (05) :1453-1463
[10]   Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver [J].
Lu, Li ;
Li, Ying ;
Kim, Soo Mi ;
Bossuyt, Wouter ;
Liu, Pu ;
Qiu, Qiong ;
Wang, Yingdi ;
Halder, Georg ;
Finegold, Milton J. ;
Lee, Ju-Seog ;
Johnson, Randy L. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (04) :1437-1442