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CSGALNACT2 restricts ovarian cancer migration and invasion by modulating MAPK/ERK pathway through DUSP1

Mingjun Ma1,2, Chao Wang1,2, Meixuan Wu3

  • 1Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, No.2699, Gaoke West Rd, Shanghai, 200092, China.

Cellular Oncology (Dordrecht, Netherlands)
|December 11, 2023
PubMed
Abstract

Insights

The Golgi transferase CSGALNACT2 acts as an ovarian cancer suppressor gene, inhibiting tumor progression and metastasis. Its downregulation correlates with poor prognosis and reduced immunotherapy benefit, suggesting its potential as a biomarker.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Ovarian cancer is a leading cause of cancer-related death in women.
  • The role and expression of the Golgi transferase CSGALNACT2 in ovarian cancer are not well understood.

Purpose of the Study:

  • To investigate the expression pattern and functional role of CSGALNACT2 in ovarian cancer.
  • To explore CSGALNACT2's potential as a prognostic biomarker and its association with immune infiltration and immunotherapy response.

Main Methods:

  • Utilized The Cancer Genome Atlas and GEPIA databases for expression analysis.
  • Employed RNA-seq, qRT-PCR, and immunohistochemistry (IHC) to validate CSGALNACT2 expression.
  • Conducted in vitro and in vivo experiments to assess CSGALNACT2's functional impact on ovarian cancer progression.
  • Performed RNA-seq, KEGG pathway analysis, and Western blotting to elucidate underlying molecular mechanisms.

Main Results:

  • CSGALNACT2 mRNA and protein levels were significantly downregulated in ovarian cancer tissues, decreasing with progression.
  • CSGALNACT2 suppressed ovarian cancer cell migration, invasion, and growth in vitro and in vivo.
  • The suppressive effect is mediated by DUSP1 modulation of the MAPK/ERK pathway.
  • CSGALNACT2 expression correlated with immune cell infiltration and demonstrated prognostic value.
  • Downregulation of CSGALNACT2 was linked to diminished benefits from immunotherapy.

Conclusions:

  • CSGALNACT2 functions as a tumor suppressor gene in ovarian cancer, inhibiting its development.
  • CSGALNACT2 holds potential as a prognostic biomarker for ovarian cancer patients.
  • Understanding CSGALNACT2's role may inform therapeutic strategies, particularly regarding immunotherapy response.
Keywords:
CSGALNACT2DUSP1MAPK/ERK pathwayMigration and invasionOvarian cancer

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