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Co-culture of Glioblastoma Stem-like Cells on Patterned Neurons to Study Migration and Cellular Interactions
Published on: February 24, 2021
Single minded 2-s (SIM2-s) gene is expressed in human GBM cells and involved in GBM invasion
Qiaowei He1, Gang Li, Yuhang Su
1Department of Neurosurgery, Qi Lu Hospital of Shandong University, Shandong Province, China.
Abstract:
The human single-minded 2 (SIM2) gene is mapped within the Down syndrome critical region (DSCR) of chromosome 21 and its short splice variant SIM2-s is suggested to be a molecular target for cancer therapy. It has been shown that SIM2-s is expressed in colon, pancreatic and prostate tumors but not in their corresponding normal tissues. In present study, we found that SIM2-s was expressed in glioma tissues as well as in glioblastoma (GBM) cell lines but not in other brain tumors or normal cortex. The invasive potential of GBM cells was significantly decreased by RNA interference targeting SIM2-s, while the proliferation was not affected. Further investigation showed that the mRNA and protein levels of matrix metalloproteinase 2 (MMP-2) were downregulated in cells treated with SIM2-s siRNA, concomitance with the upregulation of tissue inhibitor of matrix metalloproteinase 2 (TIMP-2). Moreover, the enzymatic activity of MMP-2 was clearly decreased. Our results collectively suggested that SIM2-s expressed in gliomas selectively and played a role in GBM cells invasion, which may be partly associated with the expression of MMP-2 and TIMP-2.
Insights
The single-minded 2 short variant (SIM2-s) is found in gliomas and promotes glioblastoma cell invasion. Targeting SIM2-s reduces invasion by affecting matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinase 2.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- The single-minded 2 (SIM2) gene, located in the Down syndrome critical region (DSCR) of chromosome 21, has a short splice variant (SIM2-s).
- SIM2-s is implicated as a potential cancer therapy target, with prior studies showing its expression in colon, pancreatic, and prostate tumors but not normal tissues.
Purpose of the Study:
- To investigate the role of SIM2-s in glioma development and progression.
- To determine the effect of SIM2-s on glioblastoma (GBM) cell invasion and proliferation.
Main Methods:
- Analysis of SIM2-s expression in glioma tissues and GBM cell lines.
- RNA interference (siRNA) targeting SIM2-s in GBM cells.
- Assessment of cell invasion, proliferation, and expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinase 2 (TIMP-2).
Main Results:
- SIM2-s was expressed in glioma tissues and GBM cell lines, but not in normal brain cortex or other brain tumors.
- Silencing SIM2-s significantly reduced the invasive potential of GBM cells without affecting proliferation.
- Downregulation of MMP-2 and upregulation of TIMP-2 were observed in SIM2-s-silenced cells, leading to decreased MMP-2 enzymatic activity.
Conclusions:
- SIM2-s is selectively expressed in gliomas and plays a role in GBM cell invasion.
- The invasive function of SIM2-s in GBM may be mediated through its influence on MMP-2 and TIMP-2 expression and activity.

