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| Status |
Public on Aug 11, 2020 |
| Title |
miR-24 induces human T cell exhaustion though mitochondria energy metabolic reprograming via suppressing MYC and FGF11 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Exhausted T cells (TExh) is a barrier for cancer immunotherapy, evidences demonstrate that transcriptional regulation is essential for TEX induction; however the factors that manipulate exhausted phenotype are largely unexplored. Here we showed that the microRNA (miR)-24, previously established to be enriched in eoxosmes from nasopharyngeal carcinoma (NPC) cells and promote T cell dysfunction, induced T cells to express high level of TIM-3, PD-1 and CD39 but to display low IFNg and GrB secretion and diminished proliferation ability ( a TExh phenotype) through inhibiting energy metabolism in vitro. Forced miR-24 expression inhibited ATP production through mitochondrial oxidative phosphorylation, while blockade of endogenous miR-24 the mitochondrial formation became massive and tubular and the levels of mitochondrial constituent proteins including Mfn1, Mfn2, P-Drp1 and TOMM20 was increased in OKT-3 stimulated T cells. MiR-24-mediated TEX and mitochondria metabolism reprogramming were regulated by suppressing MYC and FGF11 expression. Moreover, MYC enhanced the FGF11 transcription to promote mitochondria ATP production. Importantly, clinical data showed an increased TEX phenotype in circuiting and tumor-infiltrating T cells from NPC patients. Thus, our findings support that inhibition of miR-24-mediated mitochondria metabolism reprogramming can be titrated to break TExh immune barrier in NPC immunotherapy.
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| Overall design |
Examination of 2 different treatments in human T cells.
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| Contributor(s) |
Li J, Liu Y |
| Citation(s) |
32973789 |
| Submission date |
Feb 13, 2018 |
| Last update date |
Sep 28, 2020 |
| Contact name |
Jiang Li |
| E-mail(s) |
lijiang@sysucc.org.cn
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| Organization name |
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center
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| Street address |
Dongfengdong Road NO.651, Yuexiu District
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| City |
Guangzhou |
| State/province |
Guangdong |
| ZIP/Postal code |
510060 |
| Country |
China |
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| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA433927 |
| SRA |
SRP132772 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE110523_miR24--miR24_sponge.all.gene.txt.gz |
657.3 Kb |
(ftp)(http) |
TXT |
| GSE110523_mir24-cont-analyzed.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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