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| Status |
Public on May 26, 2023 |
| Title |
SMS2 suppresses hepatocellular carcinogenesis by impairing p85/p110 interaction |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Phosphoinositide 3-kinase (PI3K) signaling, which requires spatial compartmentalization in plasma membrane micro domains, is aberrantly activated in hepatocellular carcinoma (HCC). As a synthetic enzyme of sphingomyelin, sphingomyelin synthase 2 (SMS2) regulates membrane fluidity and microdomain structure. SMS2 functions in various diseases such as atherosclerosis, and diabetes and lung injury. However, the role of SMS2 in HCC tumorigenesis is unclear. In the present study, we found that SMS2 was substantially reduced in tumor tissues and predicted poor prognosis in HCC patients. Function assays in vitro showed that SMS2 could remarkably prevent cell proliferation, cell cycle, cell migration and invasion. Experiments in vivo revealed that SMS2-deficient mice exhibited more severe carcinogenesis and metastasis induced by diethylnitrosamine/carbon tetrachloride. The result of transcriptome sequencing showed that SMS2 was involved in PI3K/Akt signaling pathway. Further study verified that SMS2 could inhibit the expression of PI3K subunit p110α by promoting the ubiquitination of p110α. SMS2 downregulation changed lipid metabolism and PTEN distribution in lipid raft, attenuated p85α-PTEN interaction, thus promoting p85α-p110α interaction. Finally, we found that loss of SMS2 could inhibiting PTEN localization in lipid rafts. The tumor suppression effect of SMS2 on HCC cells could be rescued by p110α expression. Taken together, our findings not only demonstrates that SMS2 is a prospective tumor suppressor and prognosis indicator in HCC, but also provide understanding of the molecular mechanisms by which PI3K/AKT signaling is activated.
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| Overall design |
we compared the whole genome gene expressions of two different cell lines with and without overexpression of SMS2
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| Contributor(s) |
Tang W, Zhou Y, Li M, Meng F, Chen S, Zhang S, Yang B, Xue R, Dong L, Zhang S |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
May 26, 2022 |
| Last update date |
May 28, 2023 |
| Contact name |
Wenqing Tang |
| E-mail(s) |
13111210016@fudan.edu.cn
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| Organization name |
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Disease, Zhongshan Hospital, Fudan University
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| Street address |
180 Fenglin Road, Xuhui District
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| City |
Shanghai |
| ZIP/Postal code |
200032 |
| Country |
China |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA842681 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE204898_RAW.tar |
990.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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