Whole transcriptome and proteome analyses identify potential targets and mechanisms underlying tumor treating fields against glioblastoma.
Shengchao XuChengke LuoDikang ChenLu TangLing ChenZhixiong LiuPublished in: Cell death & disease (2022)
Glioblastoma (GBM) is one of the most malignant types of brain cancer. Tumor treating fields (TTFields) is the up-to-date treatment for GBM. However, its molecular mechanism requires additional investigation. Herein, a novel TTFields system was developed (CL-301A) and its efficiency in suppressing GBM cell proliferation and inducing cell apoptosis was demonstrated. Through the whole proteomic and transcriptomic analyses, a multitude of differentially expressed proteins (1243), mRNAs (4191), miRtNAs (47), lncRNAs (4286), and circRNAs (13,903) were identified. Bioinformatic analysis indicated that TTFields mainly affected nuclear proteins and interrupt cell mitosis-related events. Moreover, the inhibition of autophagy could significantly enhance the anti-GBM activity of TTFields. And CDK2-AS1 might be a target of TTFields to mediate cell cycle arrest via regulating CDK2 mRNA stability. This study provided valuable resources for understanding the mechanism of TTFields, which might further assist the investigation of TTFields in GBM treatment.
Keyphrases
- cell proliferation
- cell cycle
- single cell
- cell death
- cell cycle arrest
- rna seq
- signaling pathway
- stem cells
- risk assessment
- cell therapy
- genome wide
- squamous cell carcinoma
- combination therapy
- endoplasmic reticulum stress
- cerebral ischemia
- transcription factor
- young adults
- human health
- functional connectivity
- brain injury
- data analysis
- childhood cancer
- label free