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YTHDC1-mediated VPS25 regulates cell cycle by targeting JAK-STAT signaling in human glioma cells

Xiaolong Zhu1,2,3, Hui Yang1,2,3, Mengying Zhang1,2,3

  • 1Central Laboratory, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, 241001, People's Republic of China.

Cancer Cell International
|December 5, 2021
PubMed
Abstract

Insights

VPS25, a component of the endosomal sorting complex required for transport (ESCRT), is highly expressed in glioma and linked to poor prognosis. Inhibiting VPS25 suppresses glioma cell growth, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • Glioma is a prevalent malignant brain tumor with significant mortality and recurrence rates.
  • The endosomal sorting complex required for transport (ESCRT) pathway is implicated in tumorigenesis, but its precise role in glioma remains unclear.

Purpose of the Study:

  • To investigate the role of ESCRT subunits in glioma.
  • To identify potential prognostic markers and therapeutic targets for glioma.

Main Methods:

  • Bioinformatic analysis of TCGA and GEO databases to identify highly expressed ESCRT subunits in glioma.
  • In vitro functional assays to assess the impact of ESCRT subunits on glioma cell behavior.
  • Transcriptome sequencing to determine target genes and affected signaling pathways.
  • Investigation of the relationship between N6-methyladenosine (m6A) modification and ESCRT subunit expression.

Main Results:

  • VPS25 was found to be upregulated in glioma tissues, correlating with unfavorable patient prognosis.
  • VPS25 knockdown inhibited glioma cell proliferation, induced cell cycle arrest at the G0/G1 phase, and promoted apoptosis.
  • VPS25 influenced glioma cell cycle progression by regulating p21, CDK2, and cyclin E expression, and JAK-STAT signaling.
  • YTHDC1 was observed to inhibit glioma proliferation by decreasing VPS25 expression.

Conclusions:

  • VPS25 serves as a potential prognostic biomarker for glioma.
  • VPS25 represents a promising therapeutic target for glioma treatment.
Keywords:
Cell cycleGliomaJAK–STATVPS25YTHDC1

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