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Series GSE65665 Query DataSets for GSE65665
Status Public on Mar 07, 2015
Title Gene expression profiling of effect of Yap inhibition in a genetically engineered mouse model of hepatocellular carcinoma
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Defective Hippo/YAP signaling in the liver results in tissue overgrowth and development of hepatocellular carcinoma (HCC). Here, we uncover mechanisms of YAP-mediated hepatocyte reprogramming and HCC pathogenesis. We show that YAP functions as a rheostat maintaining metabolic specialization, differentiation and quiescence within the hepatocyte compartment. Importantly, treatment with siRNA-lipid nanoparticles (siRNA-LNPs) targeting YAP restores hepatocyte differentiation and causes pronounced tumor regression in a genetically engineered mouse HCC model (mice with liver-specific Mst1/Mst2 double knockout). Furthermore, YAP targets are enriched in an aggressive human HCC subtype characterized by a proliferative signature and absence of CTNNB1 mutations. Thus, our work reveals Hippo signaling as a key regulator of positional identity of hepatocytes, supports targeting YAP using siRNA-LNPs as a paradigm of differentiation-based therapy, and identifies an HCC subtype potentially responsive to this approach.
Overall design Mice with liver-specific Mst1/Mst2 double-knockout (Adeno-Cre injected Mst1-/-; Mst2Flox/Flox mice) were monitored for the formation of HCC by ultrasound imaging. Animals were then randomized to be treated by intravenous injection of either siYap-LNPs or siLuciferase-LNPs for a period of 9 days.
Contributor(s) Fitamant J, Bardeesy N, Ross KN
Citation(s) 25772357
Submission date Feb 05, 2015
Last update date May 15, 2019
Contact name Kenneth N Ross
Organization name Dana-Farber Cancer Institute
Department Pediatric Oncology
Street address 450 Brookline Ave., Rm M640
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (13)
GSM1602671 siLuc_rep1
GSM1602672 siLuc_rep2
GSM1602673 siLuc_rep3
BioProject PRJNA274661
SRA SRP053235

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE65665_JF_siLuc_vs_siYAP_D9_FPKM_150202.txt.gz 1003.9 Kb (ftp)(http) TXT
GSE65665_RAW.tar 3.4 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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