CircVPRBP inhibits nodal metastasis of cervical cancer by impeding RACK1 O-GlcNAcylation and stability

Chunyu Zhang1, Hongye Jiang1, Li Yuan1

  • 1Department of Obstetrics and Gynecology, the First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.

Oncogene
|January 19, 2023
PubMed

Insights

Loss of circVPRBP expression correlates with lymph node metastasis in cervical cancer. Restoring circVPRBP inhibits cancer spread by affecting lymphangiogenesis and RACK1 degradation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Lymph node (LN) metastasis is a critical factor in cervical cancer (CCa) progression and patient survival.
  • Circular RNAs (circRNAs) are implicated in various cancers, but their role in CCa lymph node metastasis is not well understood.

Purpose of the Study:

  • To investigate the role and mechanism of circVPRBP in cervical cancer lymph node metastasis.
  • To determine if circVPRBP can serve as a prognostic biomarker or therapeutic target for CCa.

Main Methods:

  • In vitro and in vivo experiments were conducted to assess the function of circVPRBP.
  • RfxCas13d was used for circVPRBP silencing.
  • Mechanistic studies involved investigating the interaction between circVPRBP, RACK1, and Galectin-1.

Main Results:

  • Reduced circVPRBP expression was significantly associated with LN metastasis and poorer survival in CCa patients.
  • Overexpression of circVPRBP suppressed lymphangiogenesis and LN metastasis.
  • Silencing circVPRBP promoted lymphangiogenesis and metastasis.
  • Mechanistically, circVPRBP binds RACK1, preventing O-GlcNAcylation and subsequent degradation, thereby inhibiting Galectin-1 mediated lymphangiogenesis and metastasis.

Conclusions:

  • circVPRBP acts as a tumor suppressor in CCa lymph node metastasis.
  • circVPRBP is a potential prognostic biomarker for CCa.
  • circVPRBP represents a novel therapeutic target for inhibiting CCa LN metastasis.

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