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| Status |
Public on Apr 30, 2024 |
| Title |
STC1 promotes temozolomide resistance of glioblastoma through STAT3-mediated regulation of MGMT. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Resistance to temozolomide (TMZ) is one of the major challenges for glioblastoma (GBM) therapy while the underlying mechanisms demand further exploration. Tumor-repopulating cells (TRCs) have been proven to be involved in chemotherapy resistentce. We first enriched GBM TRCs by culturing DBTRG cells in 3D soft fibrin gels and performed RNA-seq. By anlyzing the differentially expressed genes (DEGs) between TRCs and 2D conventionally cultured DBTRG cells, we identified the glycoprotein gene Stanniocalcin-1 (STC1), which is highly expressed in TRCs. Our analyses using patient data from CGGA disclosed that high STC1 expression was associated with poor prognosis, high glioma grade and TMZ therapy resistance. Both our in vitro and in vivo expreriments showed that overexpression of STC1 promoted while knockdown of STC1 inhibited GBM cell proliferation and TMZ resistance. Our mechanistic study revealed that STC1 elevated the phosphoralation of STAT3 to increase MGMT expression, which inhibited the TMZ-induced DNA damage and apoptosis. Our study provides rationale for targeting STC1 to overcome TMZ resistance.
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| Overall design |
We cultured DBTRG cells with rigid dish or soft gel, cells were harvested cells separately for RNA-seq analysis after being cultured for 5 days.
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| Contributor(s) |
Duan C, He B, Dong Z |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Mar 15, 2024 |
| Last update date |
Apr 30, 2024 |
| Contact name |
Bincan He |
| E-mail(s) |
hebincan@westlake.edu.cn
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| Organization name |
Huazhong Agricultural University
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| Street address |
1 Shizishan Rd
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| City |
Wuhan |
| ZIP/Postal code |
430070 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| GSM8148758 |
DBTRG cells, rigid dish 2D cultured, replicate 1 |
| GSM8148759 |
DBTRG cells, rigid dish 2D cultured, replicate 2 |
| GSM8148760 |
DBTRG cells, rigid dish 2D cultured, replicate 3 |
| GSM8148761 |
DBTRG cells, soft gel 3D cultured, replicate 1 |
| GSM8148762 |
DBTRG cells, soft gel 3D cultured, replicate 2 |
| GSM8148763 |
DBTRG cells, soft gel 3D cultured, replicate 3 |
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| Relations |
| BioProject |
PRJNA1088418 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE261684_TRG_vs_TRG_3D.deseq2.annot.txt.gz |
13.7 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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