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| Status |
Public on Sep 01, 2021 |
| Title |
Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
H3K36me3 catalyzed by histone methyltransferase SETD2 is one of the most conserved epigenetic marks from yeast to mammals. SETD2 is frequently mutated in multiple cancers and acts as a tumor suppressor. Here, utilizing a liver-specific deletion of Setd2 mice model, we found that Setd2 depletion is sufficient to trigger hepatocarcinoma (HCC) spontaneously. Meanwhile, in a DEN-induced HCC model, Setd2 depletion significantly promoted tumor number and size. The mechanistic study showed that Setd2 suppresses HCC not only through modulating DNA damage response, but also regulating lipid metabolism in liver. Setd2 deficiency down-regulated the expression of cholesterol efflux genes and caused lipid accumulation. ChIP-Seq analysis further revealed that Setd2 deletion induced AP-1 activation in liver, which was probably trigged by accumulated cholesterol. AP-1 is a well-known oncogene in HCC and inhibits p53 in Setd2-deficient cells. Taken together, we found the role of an important epigenetic gene in regulating cholesterol homeostasis and HCC, and revealed the underlying mechanisms.
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| Overall design |
Liver tissue or tumor mRNA profiles of 8-month old wild type (WT) and Setd2 knockout mice were generated by deep sequencing, in triplicate.
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| Contributor(s) |
Li X, Li Q, Ju L, Zhao L, Du J, Li L, Li L, Wu M |
| Citation(s) |
33058300 |
| Submission date |
Sep 03, 2019 |
| Last update date |
Dec 02, 2021 |
| Contact name |
Qinglan Li |
| E-mail(s) |
liqinglan@whu.edu.cn
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| Organization name |
Wuhan University
|
| Street address |
Room 5005, Life Science College, Wuhan University
|
| City |
Wuhan City |
| State/province |
Hubei Province |
| ZIP/Postal code |
430062 |
| Country |
China |
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| Platforms (1) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE136744 |
Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma |
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| Relations |
| BioProject |
PRJNA563560 |
| SRA |
SRP220107 |
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