Abstract
Background Gene therapy shows considerable clinical benefit in cancer therapy, in which single-stranded ribonucleic acid (siRNA) is a promising strategy in the treatment of glioblastoma (GBM). TANK-binding kinase 1 (TBK1) is critical in tumorigenesis and development, which lays a foundation for an ideal target for tumor therapy. However, the practical application of free siRNA is limited. It is urgent to develop novel strategies to deliver TBK1 siRNA to activate apoptosis and cGAS-STING pathway as a therapeutic strategy for GBM. Methods The expression and prognostic value of TBK1 were evaluated in the TCGA, CGGA, and GTEx databases. A novel gene delivery system was designed here via PEGylated reduced graphene oxide (rGO-PEG) to targeted delivery of anti-TBK1 siRNA efficiently. The efficacy of TBK1si/rGO-PEG was evaluated in GBM cells. The underlying pathways were explored by Western blot. Results TBK1 was highly expressed in glioma samples, and its high expression indicated poor prognoses in glioma patients. The rGO-PEG presented great efficiency in targeted delivery of TBK1si RNA into GBM cells with up to 97.1% transfection efficiency. TBK1si/rGO-PEG exhibited anti-GBM activities by inhibiting TBK1 and autophagy, as well as activating apoptosis and cGAS-STING pathway. Conclusion The rGO-PEG could be an efficient system facilitating the delivery of specific siRNA. TBK1si/rGO-PEG could be a novel strategy for the treatment of GBM.
Highlights
Gene therapy shows considerable clinical benefit in cancer therapy, in which single-stranded ribonucleic acid is a promising strategy in the treatment of glioblastoma (GBM)
A novel gene delivery system was designed here via PEGylated reduced graphene oxide to targeted delivery of anti-TANK-binding kinase 1 (TBK1) siRNA efficiently. e efficacy of TBK1si/rGO-PEG was evaluated in GBM cells. e underlying pathways were explored by Western blot
To preliminarily explore the potential role of TBK1 in gliomas, we extracted data from online databases including TCGA, Chinese Glioma Genome Atlas (CGGA), and Genotype-Tissue Expression (GTEx). e expression of TBK1 was significantly elevated in lower-grade glioma (LGG, grade II and III gliomas) and GBM compared with normal brain tissues (p < 0.05) (Figure 1(a))
Summary
Gene therapy shows considerable clinical benefit in cancer therapy, in which single-stranded ribonucleic acid (siRNA) is a promising strategy in the treatment of glioblastoma (GBM). It is urgent to develop novel strategies to deliver TBK1 siRNA to activate apoptosis and cGAS-STING pathway as a therapeutic strategy for GBM. A novel gene delivery system was designed here via PEGylated reduced graphene oxide (rGO-PEG) to targeted delivery of anti-TBK1 siRNA efficiently. E efficacy of TBK1si/rGO-PEG was evaluated in GBM cells. E rGO-PEG presented great efficiency in targeted delivery of TBK1si RNA into GBM cells with up to 97.1% transfection efficiency. TBK1si/rGO-PEG exhibited anti-GBM activities by inhibiting TBK1 and autophagy, as well as activating apoptosis and cGAS-STING pathway. E rGO-PEG could be an efficient system facilitating the delivery of specific siRNA. TBK1si/rGO-PEG could be a novel strategy for the treatment of GBM
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