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Status |
Public on Sep 13, 2024 |
Title |
Maintenance of magnesium homeostasis by NUF2 promotes protein synthesis and anaplastic thyroid cancer progression |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Thyroid cancer is the most frequently observed endocrine-related malignancy among which anaplastic thyroid cancer (ATC) is the most fatal subtype. The synthesis of protein is exuberant to satisfy the rapid growth of ATC tumor, but the mechanisms regulating protein synthesis are still unknown. Our research revealed that kinetochore protein NUF2 played an essential role in protein synthesis and drove the progression of ATC. The prognosis of patients with thyroid carcinoma was positively correlated with high NUF2 expression. Depletion of NUF2 in ATC cells notably inhibited the proliferation and induced apoptosis, while overexpression of NUF2 facilitated ATC cell viability and clone formation. Loss of NUF2 significantly suppressed ATC growth in both zebrafish and nude mouse models. Notably, knockdown of NUF2 epigenetically inhibited the expression of magnesium transporters through reducing the abundance of H3K4me3 at promoters, thereby reduced intracellular Mg2+ concentration. Furthermore, we found the deletion of NUF2 or magnesium transporters significantly inhibited the protein synthesis mediated by the PI3K/Akt/mTOR pathway. In conclusion, NUF2 functions as an emerging regulator for protein synthesis by maintaining the homeostasis of intracellular Mg2+, which finally drives ATC progression.
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Overall design |
To investigate the regulation of downstream genes by NUF2, we knocked down NUF2 with siRNA in 8505C cell line and then performed gene expression profiling analysis using data obtained from RNA-seq analysis.
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Contributor(s) |
Bao L, Ge M |
Citation(s) |
39242581 |
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Submission date |
Jul 16, 2024 |
Last update date |
Sep 13, 2024 |
Contact name |
Lisha Bao |
Organization name |
Zhejiang provincial people's hospital
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Street address |
Shangtang
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City |
Hangzhou |
ZIP/Postal code |
310014 |
Country |
China |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (6)
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Relations |
BioProject |
PRJNA1136534 |
Supplementary file |
Size |
Download |
File type/resource |
GSE272374_genes_fpkm_expression.txt.gz |
8.9 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
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