Rac GTPase activating protein 1 promotes the glioma growth by regulating the expression of MCM3

Autor: Bo Jia, Yuran Jiang, Yu Huan, Yu Han, Wei Liu, Xiao Liu, Yingwen Wang, Lei He, Zhengcong Cao, Xin He, Kuo Zhang, Jintao Gu, Qingdong Guo, Zhou Fei
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Translational Oncology, Vol 37, Iss , Pp 101756- (2023)
Druh dokumentu: article
ISSN: 1936-5233
DOI: 10.1016/j.tranon.2023.101756
Popis: Glioma is the most common tumor of the nervous system. The diffuse growth and proliferation of glioma poses great challenges for its treatment. Here, Transcriptomic analysis revealed that Rac GTPase activating protein 1 (RACGAP1) is highly expressed in glioma. RACGAP1 has been shown to play an important role in the malignant biological progression of a variety of tumors. However, the underlying role and mechanism in glioma remain poorly understood. By using quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry and Orthotopic mouse xenografts, we confirmed that knockdown of RACGAP1 impeded cell proliferation in glioma and prolonged the survival of orthotopic mice. Interestingly, we also found that inhibiting the expression of RACGAP1 reduced the expression of minichromosome maintenance 3 (MCM3) through RNA-seq and rescue assay, while Yin Yang 1 (YY1) transcriptionally regulated RACGAP1 expression. Furthermore, T7 peptide-decorated exosome (T7-exo) is regard as a promising delivery modality for targeted therapy of glioma, and the T7-siRACGAP1-exo significantly improved the survival time of glioma bearing mice. These results suggested that targeting RACGAP1 may be a potential strategy for glioma therapy.
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