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GEO help: Mouse over screen elements for information. |
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Status |
Public on Mar 01, 2024 |
Title |
SPARC boost cholesterol-dependent aggressive phenotype and sorafenib resistance in hepatocellular carcinoma |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is characterized as a highly aggressive tumor entity and has become a health challenge worldwide. Intracellular secreted protein acidic and rich in cysteine (SPARC) has been described as secreted protein that serves as paracrine mediator between cells extracellular matrix (ECM), however, its intracellular role remains unclear. Genetically modified HCC cell lines, cancer patient-derived organoids, and mouse models were used to analyze SPARC on metabolic processes, as well as the invasive behavior and sorafenib resistance of HCC cells. Transcriptome, interactome, and biochemical analyses were performed to study how SPARC regulate cholesterol homeostasis. High expression of intracellular SPARC was significantly associated with elevated cholesterol levels and an enhanced invasive phenotype in HCC. Our findings unveil a previously unrecognized interplay between SPARC and cholesterol homeostasis. Targeting SPARC-triggered cholesterol-dependent oncogenic signaling serves as a promising strategy for treating advanced HCC.
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Overall design |
To investigate the impact of SPARC overexpression on cholesterol metabolism and PI3K-AKT signaling in HCC cell lines and tumor tissues. HepG2 cells stably expressing SPARC were generated by lentiviral vector system. HepG2 cells transfected with empty vector served as a negative control. Three biological replications were performed to assess the transcriptome in SPARC-overexpression cells relative to the control HepG2 cells.
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Contributor(s) |
Wu H, Wan S |
Citation(s) |
38471084 |
Submission date |
Aug 14, 2023 |
Last update date |
Jun 03, 2024 |
Contact name |
Shan Wan |
E-mail(s) |
shanwan5@suda.edu.cn
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Organization name |
Soochow University
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Department |
Pathology
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Street address |
Renai Road 199
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City |
Suzhou |
ZIP/Postal code |
215000 |
Country |
China |
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Platforms (1) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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Samples (6)
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GSM7708656 |
HepG2 cells expressing empty vector, replicate 1 |
GSM7708657 |
HepG2 cells expressing empty vector, replicate 2 |
GSM7708658 |
HepG2 cells expressing empty vector, replicate 3 |
GSM7708659 |
HepG2 cells with hSPARC overexpression, replicate 1 |
GSM7708660 |
HepG2 cells with hSPARC overexpression, replicate 2 |
GSM7708661 |
HepG2 cells with hSPARC overexpression, replicate 3 |
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Relations |
BioProject |
PRJNA1005188 |
Supplementary file |
Size |
Download |
File type/resource |
GSE240747_mRNA_Expression_Profiling-SPARC_HepG2.xlsx |
5.1 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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