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| Status |
Public on Sep 01, 2024 |
| Title |
Gene expression profiling of CD8+ T cells in the Norathyriol versus PBS-treated co-culture system |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Metabolic reprogramming fuels cancer cell metastasis and remodels the immunosuppressive tumor microenvironment (TME). We report here that a circRNA, circPETH, packaged by extracellular vesicles (EVs) from tumor-associated macrophages (TAMs) to hepatocellular carcinoma (HCC) cells, facilitates glycolysis and metastasis of recipient HCC cells. Mechanistically, circPETH-147aa, encoded by circPETH in a m6A-driven manner, promotes PKM2-catalyzed ALDOA-S36 phosphorylation via MEG pocket. Furthermore, circPETH-147aa impairs anti-HCC immunity by elevating HuR-dependent SLC43A2 mRNA stability and driving methionine and leucine deficiency in cytotoxic CD8+ T cells. Importantly, by virtual and experimental screening, we found that the novel small-molecule Norathyriol was an effective inhibitor that targets the MEG pocket on circPETH-147aa surface. Norathyriol reverses circPETH-147aa-facilitated acquisition of metabolic and metastatic phenotypes for HCC cells, increases anti-PD1 efficacy and boosts cytotoxic CD8+ T-cell function. Our findings determine Norathyriol as a promising anti-HCC agent that contributes to the attenuation of advanced HCC resistance to immune checkpoint blocker (ICB) therapies.
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| Overall design |
To understand the mechanistic association of Norathyriol with CD8+ T cells, RNA-seq was performed to compare the expression profiles of CD8+ T cells in the Norathyriol versus PBS-treated co-culture system.
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| Contributor(s) |
Lan T, Gao F, Cai Y |
| Citation missing |
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| |
| Submission date |
Sep 01, 2023 |
| Last update date |
Sep 01, 2024 |
| Contact name |
Tian Lan |
| E-mail(s) |
blue_sky_land@163.com
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| Organization name |
West China Hospital
|
| Department |
Department of Liver Surgery & Liver Transplantation
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| Lab |
Laboratory of Liver Surgery
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| Street address |
No. 37 of Guoxue Lane
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| City |
Chengdu |
| State/province |
Sichuan |
| ZIP/Postal code |
610041 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1011824 |
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