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| Status |
Public on Apr 13, 2020 |
| Title |
Defects in mTORC1 Network and mTORC1-STAT3 Pathway Crosstalk Contributes to Noninflammatory Hepatocellular Carcinoma |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
mTORC1-driven noninflammatory HCC and provide insight into further development of a protective strategy against noninflammatory HCC.
Background & Aims: Mammalian target of rapamycin complex 1 (mTORC1) is frequently hyperactivated in hepatocellular carcinoma (HCC). Cases of HCC without inflammation and cirrhosis are not rarely seen in clinics. However, the molecular basis of noninflammatory HCC remains unclear.
Methods: Spontaneous noninflammatory HCC in mice was triggered by constitutive elevation of mTORC1 by liver-specific Tsc1 knockout (LTsc1KO). A multi-omics approach was utilized on tumor tissues to better understand the molecular basis for the development of HCC in the LTsc1KO model.
Results: We showed that LTsc1KO in mice triggered spontaneous noninflammatory HCC, with molecular characteristics similar to those of diethylnitrosamine-mediated noncirrhotic HCC. Mitochondrial and autophagy defects, as well as hepatic metabolic disorder were manifested in HCC development by LTsc1KO. mTORC1 activation on its own regulated an oncogenic network (DNA-damage-inducible transcript 4, nuclear protein 1 and fibroblast growth factor 21), and mTORC1–signal transducer and activator of transcription pathway crosstalk that altered specific metabolic pathways contributed to the development of noninflammatory HCC.
Conclusion: Our findings reveal the mechanisms of mTORC1-driven noninflammatory HCC and provide insight into further development of a protective strategy against noninflammatory HCC.
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| Overall design |
Spontaneous noninflammatory HCC in mice was triggered by constitutive elevation of mTORC1 by liver-specific Tsc1 knockout (LTsc1KO). A multi-omics approach was utilized on tumor tissues to better understand the molecular basis for the development of HCC in the LTsc1KO model.
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| Contributor(s) |
Li T, Gao Y |
| Citation missing |
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| Submission date |
Mar 22, 2020 |
| Last update date |
Apr 15, 2020 |
| Contact name |
Ting Li |
| E-mail(s) |
harazawarui520lt@sina.com
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| Phone |
+86 15013097752
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| Organization name |
Southern Medical University
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| Department |
Department of Hepatobiliary Surgery II, Zhujiang Hospital
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| Lab |
Institute of Regenerative Medicine
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| Street address |
253 Gongye Street
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| City |
Guangzhou |
| State/province |
Guangdong |
| ZIP/Postal code |
510280 |
| Country |
China |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA613942 |
| SRA |
SRP253644 |
