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| Status |
Public on Nov 17, 2022 |
| Title |
Upregulation of MTHFD2 is associated with PD-L1 activation in bladder cancer via the PI3K/AKT pathway |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) has been implicated in the etiology of various human malignant tumors, although its exact role in bladder cancer (BC) remains to be explored. The present study determined the upregulation of MTHFD2 in BC tissues using expression data from The Cancer Genome Atlas (TCGA), a commercial BC tissue microarray (TMA) and patients’ tissues collected by surgery. MTHFD2 expression in patients with BC was frequently associated with worse prognosis, tumor immune cell infiltration and programmed death-ligand 1 (PD-L1) expression. Next, using small interfering RNA, the expression of MTHFD2 in BC cell lines was knocked down, and the results revealed that the tumor cell proliferation and colony-formation abilities were greatly reduced, as well as the expression of PD-L1. In a xenograft nude mouse model, these findings were confirmed. Simultaneously, it was found that abnormal expression of MTHFD2 was closely associated with the PI3K/AKT signaling pathway in both RNA-sequencing and TCGA datasets. This observation was verified in vitro by detecting the protein expression of PI3K and AKT. The activation of PI3K and AKT was enhanced after stimulation with 740Y-P, a PI3K activator, and their cellular activities and PD-L1 expression levels were restored. Finally, it was found that the MTHFD2 levels were positively correlated with chemosensitivity to traditional BC chemotherapeutic agents and various PI3K-AKT-targeted drugs by analyzing the Genomics of Drug Sensitivity in Cancer (GDSC) database. Overall, the present findings revealed that elevation of MTHFD2 was associated with PD-L1 activation in BC via the PI3K/AKT signaling pathway, suggesting that it could be a promising marker of chemotherapy and immunotherapy for BC.
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| Overall design |
The MTHFD2 gene was knocked out in bladder cancer cell lines, and the differentially expressed genes and regulated signaling pathways were analyzed by sequencing. Finally, the results were verified by in vitro experiments.
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| Contributor(s) |
Deng X, Liu X, Hu B, Liu J |
| Citation(s) |
36601741 |
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| Submission date |
Nov 11, 2022 |
| Last update date |
Feb 10, 2023 |
| Contact name |
Bin Fu |
| Organization name |
The First Affiliated Hospital of Nanchang Universi
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| Department |
department of urology
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| Street address |
No.17, Yong Wai Zheng Street, Donghu Districtstrict,
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| City |
Nanchang |
| State/province |
Jiangxi |
| ZIP/Postal code |
330006 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| GSM6726681 |
T24-NC-1,bladder cancer cell lines T24 cell, control group, rep1 |
| GSM6726682 |
T24-NC-2,bladder cancer cell lines T24 cell, control group, rep2 |
| GSM6726683 |
T24-NC-3,bladder cancer cell lines T24 cell, control group, rep3 |
| GSM6726684 |
T24-shRNA2-1,bladder cancer cell lines T24 cell, MTHFD2-shRNA2, rep1 |
| GSM6726685 |
T24-shRNA2-2,bladder cancer cell lines T24 cell, MTHFD2-shRNA2, rep2 |
| GSM6726686 |
T24-shRNA2-3,bladder cancer cell lines T24 cell, MTHFD2-shRNA2, rep3 |
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| Relations |
| BioProject |
PRJNA900546 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE217785_All.counts.txt.gz |
369.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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