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

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.