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.


CONCLUSIONS
miR-375 is an important regulator of YAP oncogene, implicating a potential therapeutic role in HCC treatment.
Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, China.
Angela M
AM
Liu
Ronnie T P
RT
Poon
John M
JM
Luk
D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008156:Luciferases / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D018797:Cell Cycle Proteins; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D014157:Transcription Factors; C456659:YY1AP1 protein, human; D008156:Luciferases