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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
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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 NFB 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.
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Overall design |
Five non-tumor and five tumor biopsy samples were obtained and their transcriptional profiles compared.
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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 |
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Submission date |
Feb 27, 2020 |
Last update date |
Dec 09, 2022 |
Contact name |
Supriyo De |
Organization name |
NIA-IRP, NIH
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Department |
Laboratory of Genetics and Genomics
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Lab |
Computational Biology & Genomics Core
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Street address |
251 Bayview Blvd
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City |
Baltimore |
State/province |
Maryland |
ZIP/Postal code |
21224 |
Country |
USA |
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Platforms (1) |
GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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Samples (12)
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Relations |
BioProject |
PRJNA609169 |
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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