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Series GSE68778 Query DataSets for GSE68778
Status Public on May 31, 2017
Title Targeting of WEE1 suppresses tumorigenecity and cancer stem cell-like phenotype in hepatocellular carcinoma
Organism Homo sapiens
Experiment type Expression profiling by array
Summary The current standard-of-care for advanced liver cancer is limited. Therefore, there is an urgent need for development of novel molecular targeted therapy. Increase of WEE1 kinase activity through an epigenetic regulation plays an important role in the development of hepatocellular carcinoma (HCC). Here we demonstrated that WEE1 siRNA silencing caused inhibition of HCC cell growth through blockade of cell cycle progression and induction of apoptosis. The anti-proliferative effects were driven by a subset of molecular alterations including the upregulation of cdk inhibitor p21 and the downregulation of AKT1, CDK2, cyclin B1 (CCNB1), PARP1 and GPAM which are functionally involved in control of cell cycle, apoptosis and lipid metabolism. Systemic delivery of a modified WEE1 siRNA encapsulated in lipid nanoparticles significantly inhibited human HCC growth in murine xenograft models, and increased mice survival. Wee1 silencing in tumor cells also resulted in a strong inhibition of lipogenesis (SREBP1C, FAS) and caused a marked decrease in fat accumulation. Of importance, knockdown of WEE1 dramatically reduced the portion of liver cancer stem cells (CSCs) population through co-downregulation of cancer stemness genes and weakened the capacity of sphere formation and the ability of cancer cell migration. Our findings suggest that the epigenetic modifier WEE1 functionally involve to HCC lipid metabolism and CSC-like phenotype maintenance and that molecular targeting of WEE1 may be an effective systemic therapy for prevention of tumor recurrence via elimination of CSCs in liver tumor microenvironment.
 
Overall design HepG2 cells were treated with WEE1 siRNA and negative control siRNA for 48 hours and subjected to illumina microarray analysis.
 
Contributor(s) Lee Y, Seo D, Thorgeirsson SS
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Submission date May 12, 2015
Last update date May 31, 2017
Contact name Daekwan Seo
E-mail(s) daekwan.seo@psomagen.com
Phone +1-301-251-1007
Organization name Psomagen Inc
Department Bioinformatics
Lab BI
Street address 1330 Piccard Dr., Ste 103
City Rockville
State/province MARYLAND
ZIP/Postal code 20850
Country USA
 
Platforms (1)
GPL6883 Illumina HumanRef-8 v3.0 expression beadchip
Samples (8)
GSM1681194 Negative Control siRNA rep1
GSM1681195 Negative Control siRNA rep2
GSM1681196 Negative Control siRNA rep3
Relations
BioProject PRJNA283859

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE68778_RAW.tar 3.9 Mb (http)(custom) TAR
GSE68778_non-normalized_data.txt.gz 2.1 Mb (ftp)(http) TXT
Processed data included within Sample table

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