Jia Bo, Jiang Yuran, Huan Yu, Han Yu, Liu Wei, Liu Xiao, Wang Yingwen, He Lei, Cao Zhengcong, He Xin, Zhang Kuo, Gu Jintao, Guo Qingdong, Fei Zhou
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China; State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Pediatric Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China.
Transl Oncol. 2023 Nov;37:101756. doi: 10.1016/j.tranon.2023.101756. Epub 2023 Aug 16.
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.
胶质瘤是神经系统最常见的肿瘤。胶质瘤的弥漫性生长和增殖对其治疗构成了巨大挑战。在此,转录组分析显示Rac GTP酶激活蛋白1(RACGAP1)在胶质瘤中高表达。RACGAP1已被证明在多种肿瘤的恶性生物学进展中发挥重要作用。然而,其在胶质瘤中的潜在作用和机制仍知之甚少。通过使用定量实时聚合酶链反应(qRT-PCR)、蛋白质印迹法、免疫组织化学和原位小鼠异种移植,我们证实敲低RACGAP1可阻碍胶质瘤细胞增殖并延长原位小鼠的生存期。有趣的是,我们还发现通过RNA测序和拯救试验抑制RACGAP1的表达可降低微小染色体维持蛋白3(MCM3)的表达,而阴阳1(YY1)转录调控RACGAP1的表达。此外,T7肽修饰的外泌体(T7-exo)被认为是一种有前景的胶质瘤靶向治疗递送方式,且T7-siRACGAP1-exo显著延长了荷瘤小鼠的生存时间。这些结果表明,靶向RACGAP1可能是一种潜在的胶质瘤治疗策略。