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
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