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Series GSE146049 Query DataSets for GSE146049
Status Public on Dec 08, 2022
Title NIK/MAP3K14 in hepatocytes orchestrates NASH to hepatocellular carcinoma progression via JAK2/STAT5 inhibition
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Nonalcoholic fatty liver disease (NAFLD) ranges from steatosis to nonalcoholic steatohepatitis (NASH), that often progresses to hepatocellular carcinoma (HCC) through a largely undefined mechanism. NASH and HCC both depend on inflammatory signaling whose master regulator is the NFκB transcription factor family, activated by canonical and non-canonical pathways. Here, we investigated non-canonical NFκB-inducing kinase (NIK/MAP3K14) in metabolic NASH, NASH to HCC transition as well as in DEN-induced HCC. We revealed that hepatocyte-specific NIK deficiency (NIKLKO) ameliorated metabolic NASH complications and reduced hepatocarcinogenesis however, independent of its role in NFB pathway. Instead, hepatic NIK attenuated hepatoprotective JAK2/STAT5 signaling that is a prerequisite for NASH and NASH to HCC progression in mice and humans. Our data suggest NIK-mediated inhibitory JAK2 phosphorylation at serine 633 that might be amenable for future therapeutic interventions in patients.
 
Overall design Five non-tumor and five tumor biopsy samples were obtained and their transcriptional profiles compared.
 
Contributor(s) Vesting AJ, Jais A, Klemm P, Steuernagel L, Wienand P, Fog-Tonnesen M, Hvid H, Fog-Tonnesen A, Kukat C, Nolte H, Georgomanolis T, Pasparakis J, Pasparakis M, Schmidt A, Krüger M, Supprian MS, Waisman A, Straub BK, Raschzok N, Bernier M, Birkenfeld A, Hövelmeyer N, Brüning JC, Wunderlich FT
Citation(s) 36356831
Submission date Feb 27, 2020
Last update date Dec 09, 2022
Contact name Supriyo De
Organization name NIA-IRP, NIH
Department Laboratory of Genetics and Genomics
Lab Computational Biology & Genomics Core
Street address 251 Bayview Blvd
City Baltimore
State/province Maryland
ZIP/Postal code 21224
Country USA
 
Platforms (1)
GPL10558 Illumina HumanHT-12 V4.0 expression beadchip
Samples (12)
GSM4363489 Non_tumor_Liver_replicate_1
GSM4363490 Non_tumor_Liver_replicate_1_TR
GSM4363491 Non_tumor_Liver_replicate_2
Relations
BioProject PRJNA609169

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE146049_RAW.tar 26.2 Mb (http)(custom) TAR
GSE146049_non-normalized_data.txt.gz 1.9 Mb (ftp)(http) TXT
Processed data included within Sample table

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