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NF2 Gene Participates in Regulation of the Cell Cycle of Meningiomas by Restoring Spindle Assembly Checkpoint Function and Inhibiting the Binding of Cdc20 Protein to Anaphase Promoting Complex/Cyclosome
- Source :
- World Neurosurgery. 158:e245-e255
- Publication Year :
- 2022
- Publisher :
- Elsevier BV, 2022.
-
Abstract
- Background The neurofibromatosis type 2 (NF2) gene mutation is the leading genetic event in meningiomas, usually accompanied by malignant features. Dysfunction of the spindle assembly checkpoint (SAC) induces tumorigenesis. However, the crosstalk between NF2 and SAC in meningiomas remains unclear. Methods Cell proliferation, invasion, apoptosis, and cell cycle of meningiomas were determined by cell counting kit-8 assay, transwell assay, and flow cytometry, respectively. The expression of SAC in meningioma cells was detected by quantitative real-time polymerase chain reaction and Western blot. The interaction between anaphase promoting complex/cyclosome (APC/C) and cell division cycle 20 (Cdc20) protein in meningioma cells was further explored by co-immunoprecipitation. Results We found that the expression of NF2/merlin was low or absent in malignant meningiomas. Overexpression of NF2 suppressed the proliferation and invasion of meningioma cells, prolonged the G2/M phase, and elevated the expression of SAC proteins at posttranscription. Furthermore, the interaction between APC/C and Cdc20 was inhibited by NF2. Conclusions Our findings suggested that NF2 might restore SAC function by impairing the binding of APC/C and Cdc20, thereby limiting the mitotic rate and inhibiting proliferation of meningiomas.
- Subjects :
- Cdc20 Proteins
Cell Cycle Proteins
Spindle Apparatus
CDC20
Gene mutation
Anaphase-Promoting Complex-Cyclosome
Meningioma
Genes, Neurofibromatosis 2
Meningeal Neoplasms
otorhinolaryngologic diseases
Humans
Medicine
neoplasms
Neurofibromin 2
business.industry
Cell growth
Cell Cycle
Cell cycle
medicine.disease
nervous system diseases
Cell biology
Merlin (protein)
Spindle checkpoint
M Phase Cell Cycle Checkpoints
Surgery
Neurology (clinical)
Anaphase-promoting complex
business
Subjects
Details
- ISSN :
- 18788750
- Volume :
- 158
- Database :
- OpenAIRE
- Journal :
- World Neurosurgery
- Accession number :
- edsair.doi.dedup.....842f0f7da9d77cbb586f201e3f3330cb