| Title |
SIL1 functions as an oncogene in glioma by AKT/mTOR signaling pathway
|
|---|---|
| Published in |
OncoTargets and therapy, July 2018
|
| DOI | 10.2147/ott.s167552 |
| Pubmed ID | |
| Authors |
Hao Xu, Shangchen Xu, Rui Zhang, Tao Xin, Qi Pang |
| Abstract |
SIL1 is a ubiquitous protein localized to the endoplasmic reticulum and functions as a cochaperone of BiP. Previous studies have shown that function loss of SIL1 is often associated with neurological diseases, such as Marinesco-Sjögren Syndrome. However, no studies have investigated the function of SIL1 in tumors. In this study we aim to reveal functions of SIL1 and the underlying mechanisms in glioma. First, by searching on Gene Expression Profiling Interactive Analysis, we examined SIL1 expression and prognostic value in glioblastoma multiforme (GBM) and brain lower grade glioma (LGG). Immunohistochemical analysis (IHC) was also performed to determine the endogenic SIL1 level. Cell counting kit-8 (CCK8) and clone formation assays were used to detect cell proliferation of U251 cells. Cell migration was detected by transwell assay and cell cycle and apoptosis were detected by flow cytometry. Western blot was performed to determine protein expression. We found that the expression of SIL1 was increased by approximately 1.5-fold in GBM and 1.3-fold in LGG compared with normal controls (P<0.05) and negatively correlated with patients' survival. IHC revealed that SIL1 expression was significantly higher in glioma tissues than that in paracancerous tissues (P<0.05). Glioma patients with high SIL1 expression accounted for 65.79% (25/38) of total samples and SIL1 expression significantly increased in grade IV glioma compared to grades I-III (P=0.026). Suppression of SIL1 expression led to significant inhibition of U251 cell proliferation. Transwell assay showed that cell migration of U251 was significantly inhibited by siSIL transfection, with an inhibitory rate reaching 69%. Flow cytometry detection showed that siSIL1 could induce apoptosis of U251 cells and upregulated the expression of the pro-apoptotic protein Bax and Caspase3-P17. However, siSIL1 transfection had no effect on the cell cycle. Mechanism studies demonstrated that siSIL1 transfection led to inactivation of AKT/mTOR signaling pathway, including decreased phosphorylation of AKT and mTOR without affecting protein expression, as well as decreased expression of the downstream effector p70S6K. Downregulation of SIL1 inhibited the progression of glioma by suppressing the AKT/mTOR signaling pathway. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Portugal | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 9 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 9 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 4 | 44% |
| Student > Ph. D. Student | 1 | 11% |
| Student > Doctoral Student | 1 | 11% |
| Student > Master | 1 | 11% |
| Unknown | 2 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 5 | 56% |
| Psychology | 1 | 11% |
| Biochemistry, Genetics and Molecular Biology | 1 | 11% |
| Unknown | 2 | 22% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 July 2018.
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#22,767,715
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Outputs from OncoTargets and therapy
#2,078
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#299,743
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Outputs of similar age from OncoTargets and therapy
#80
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