Simple Summary Malignant meningiomas have high aggressiveness and recurrence rates and a poor prognosis, with no clear pharmacological treatment available. The study aims to investigate the progression mechanism of malignant meningiomas and the targets of intervention. RACK1 and CSNK2B have been shown to promote tumor progression but their roles in meningiomas are not clear. In this study, we will investigate the roles of RACK1-CSNK2B in meningiomas and search for targets to inhibit the progression of meningiomas.Abstract Higher-grade meningiomas (WHO grade II and III) are characterized by aggressive invasiveness and high postoperative recurrence rates. The prognosis remains inadequate even with adjuvant radiotherapy and currently there is no definitive pharmacological treatment strategy and target for malignant meningiomas. This study aims to unveil the mechanisms driving the malignant progression of meningiomas and to identify potential inhibitory targets, with significant clinical implications. Implementing techniques such as protein immunoprecipitation, mass spectrometry, RNA interference, and transcriptome sequencing, we investigated the malignancy mechanisms in meningioma cell lines IOMM-LEE and CH157-MN. Additionally, in vivo experiments were carried out on nude mice. We discovered a positive correlation between meningioma malignancy and the levels of the receptor for activated C kinase 1 (RACK1), which interacts with CSNK2B, the beta subunit of casein kinase 2 (CK2), inhibiting its ubiquitination and subsequent degradation. This inhibition allows CK2 to activate the NF-kappa b pathway, which increases the transcription of CDK4 and cyclin D3, resulting in the transition of the cell cycle into the G2/M phase. The RACK1 inhibitor, harringtonolide (HA), significantly suppressed the malignant tendencies of meningioma cells. Our study suggests that RACK1 may play a role in the malignant progression of meningiomas, and therefore, targeting RACK1 could emerge as an effective strategy for reducing the malignancy of these tumors.
基金：
This research was funded by the National Natural Science Foundation of China, grant
number 82173136.
第一作者单位：[1]Huazhong Univ Sci & Technol,Dept Neurosurg,Tongji Med Coll,Tongji Hosp,Wuhan 430030,Peoples R China[2]Huazhong Univ Sci & Technol,Sino German Neurooncol Mol Lab,Tongji Med Coll,Tongji Hosp,Wuhan 430030,Peoples R China[3]Huazhong Univ Sci & Technol, Hubei Key Lab Neural Injury & Funct Reconstruct, Wuhan 430030, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Huazhong Univ Sci & Technol,Dept Neurosurg,Tongji Med Coll,Tongji Hosp,Wuhan 430030,Peoples R China[2]Huazhong Univ Sci & Technol,Sino German Neurooncol Mol Lab,Tongji Med Coll,Tongji Hosp,Wuhan 430030,Peoples R China[3]Huazhong Univ Sci & Technol, Hubei Key Lab Neural Injury & Funct Reconstruct, Wuhan 430030, Peoples R China
推荐引用方式(GB/T 7714)：
Maalim Ali Abdi,Wang Zihan,Huang Yimin,et al.RACK1 Promotes Meningioma Progression by Activation of NF-κB Pathway via Preventing CSNK2B from Ubiquitination Degradation[J].CANCERS.2024,16(4):doi:10.3390/cancers16040767.
APA：
Maalim, Ali Abdi,Wang, Zihan,Huang, Yimin&Lei, Ting.(2024).RACK1 Promotes Meningioma Progression by Activation of NF-κB Pathway via Preventing CSNK2B from Ubiquitination Degradation.CANCERS,16,(4)
MLA：
Maalim, Ali Abdi,et al."RACK1 Promotes Meningioma Progression by Activation of NF-κB Pathway via Preventing CSNK2B from Ubiquitination Degradation".CANCERS 16..4(2024)
