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.
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.
摘要：
背景：2型神经纤维瘤病（NF2）基因突变是脑膜瘤的主要遗传事件，通常伴有恶性特征。主轴组装检查点(SAC)的功能障碍诱导肿瘤发生。然而,脑膜瘤中NF2和SAC之间的串扰仍不清楚。
方法：细胞增殖，入侵,凋亡，通过细胞计数试剂盒-8测定脑膜瘤的细胞周期，transwell分析，和流式细胞术，分别。通过实时定量聚合酶链反应和Westernblot检测脑膜瘤细胞中SAC的表达。通过免疫共沉淀进一步研究了脑膜瘤细胞中后期促进复合物/环小体（APC/C）与细胞分裂周期20（Cdc20）蛋白之间的相互作用。
结果：我们发现NF2/merlin在恶性脑膜瘤中的表达较低或不存在。NF2过表达抑制脑膜瘤细胞的增殖和侵袭,延长G2/M阶段，并在转录后提高SAC蛋白的表达。此外，NF2抑制了APC/C与Cdc20的相互作用。
结论：我们的研究结果表明，NF2可能通过削弱APC/C和Cdc20的结合来恢复SAC功能，从而限制有丝分裂率并抑制脑膜瘤的增殖。
方法：细胞增殖，入侵,凋亡，通过细胞计数试剂盒-8测定脑膜瘤的细胞周期，transwell分析，和流式细胞术，分别。通过实时定量聚合酶链反应和Westernblot检测脑膜瘤细胞中SAC的表达。通过免疫共沉淀进一步研究了脑膜瘤细胞中后期促进复合物/环小体（APC/C）与细胞分裂周期20（Cdc20）蛋白之间的相互作用。
结果：我们发现NF2/merlin在恶性脑膜瘤中的表达较低或不存在。NF2过表达抑制脑膜瘤细胞的增殖和侵袭,延长G2/M阶段，并在转录后提高SAC蛋白的表达。此外，NF2抑制了APC/C与Cdc20的相互作用。
结论：我们的研究结果表明，NF2可能通过削弱APC/C和Cdc20的结合来恢复SAC功能，从而限制有丝分裂率并抑制脑膜瘤的增殖。
