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 fi...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2010-04, Vol.394 (3), p.623-627
Main Authors: Liu, Angela M., Poon, Ronnie T.P., Luk, John M.
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
Base Sequence
CARCINOGENESIS
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - pathology
Carcinoma, Hepatocellular - therapy
Cell Line, Tumor
CELL PROLIFERATION
Female
Gene Expression Regulation, Neoplastic
GENE REGULATION
Genes, Reporter
Hepatocellular carcinoma
HEPATOMAS
Hippo signaling
Humans
LIVER
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Liver Neoplasms - therapy
LUCIFERASE
Luciferases - genetics
Male
MicroRNA
MicroRNAs - genetics
MicroRNAs - metabolism
Neoplasm Invasiveness
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
ONCOGENES
PATIENTS
Transcription Factors - genetics
Transcription Factors - metabolism
YAP
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2010.03.036