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Biochem Biophys Res Commun. 2010 Apr 9;394(3):623-7. doi: 10.1016/j.bbrc.2010.03.036. Epub 2010 Mar 10.

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

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  • 1Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, China.

Abstract

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.

Copyright 2010 Elsevier Inc. All rights reserved.

[PubMed - indexed for MEDLINE]
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