Abstract
BackgroundGlioma is a common type of malignant brain tumor with a high mortality and relapse rate. The endosomal sorting complex required for transport (ESCRT) has been reported to be involved in tumorigenesis. However, the molecular mechanisms have not been clarified.MethodsBioinformatics was used to screen the ESCRT subunits highly expressed in glioma tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The function of the ESCRT subunits in glioma cells was examined in vitro. Transcriptome sequencing analyzed the target genes and signaling pathways affected by the ESCRT subunit. Finally, the relationship between m6A (N6-methyladenosine) modification and high expression of the ESCRT subunit was studied.ResultsVPS25 was upregulated in glioma tissues, which was correlated with poor prognosis in glioma patients. Furthermore, VPS25 knockdown inhibited the proliferation, blocked the cell cycle, and promoted apoptosis in glioma cells. Meanwhile, VPS25 induced a G0/G1 phase arrest of the cell cycle in glioma cells by directly mediating p21, CDK2, and cyclin E expression, and JAK-signal transducer and activator of transcription (STAT) activation. Finally, YTHDC1 inhibited glioma proliferation by reducing the expression of VPS25.ConclusionThese results suggest that VPS25 is a promising prognostic indicator and a potential therapeutic target for glioma.
Highlights
Glioma is a common type of malignant brain tumor with a high mortality and relapse rate
VPS25 is one subunit of the endosomal sorting complex required for transport (ESCRT) [6]
Screening for highly expressed ESCRT subunits in glioma To examine the function of the ESCRT complex in glioma tumorigenesis, the expression of main ESCRT subunits was screened from two databases: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) (Additional file 1: Fig. S1 and Additional file 2: Fig. S2)
Summary
Glioma is a common type of malignant brain tumor with a high mortality and relapse rate. The endosomal sorting complex required for transport (ESCRT) has been reported to be involved in tumorigenesis. The molecular mechanisms have not been clarified. Glioma refers to a tumor originating from glial cells. It is the most common tumor in the central nervous system (CNS) and has the highest lethal rate [1]. Exploring the underlying molecular mechanisms associated with glioma progression and metastasis may contribute to discovering more effective treatment methods and targets. VPS25 is one subunit of the endosomal sorting complex required for transport (ESCRT) [6]. ESCRT is the molecular machinery in eukaryotic cells that recognizes the ubiquitinated cargo at the intraluminal vesicles (ILVs) and sorts them into late endosomes to form multivesicular bodies (MVBs). The ESCRT-II complex comprises the VPS25, VPS22, and VPS36 subunits [11]
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