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Poly C Binding Protein 1 Regulates p62/SQSTM1 mRNA Stability and Autophagic Degradation to Repress Tumor Progression

Wenliang Zhang1,2, Shaoyang Zhang2, Wen Guan2

  • 1Translational Medicine Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Frontiers in Genetics
|September 14, 2020
PubMed

Insights

Poly C Binding Protein 1 (PCBP1) acts as a tumor suppressor by inhibiting autophagy and promoting apoptosis in ovarian cancer. Its downregulation correlates with tumor progression, suggesting therapeutic targeting of autophagy.

Area of Science:

  • Molecular Oncology
  • Cellular Biology
  • Cancer Research

Background:

  • Poly C Binding Protein 1 (PCBP1) is recognized as a tumor suppressor, frequently deleted in various cancers.
  • The precise mechanisms underlying PCBP1's tumor suppressive functions, particularly in ovarian cancer, remain largely unelucidated.

Purpose of the Study:

  • To investigate the role of PCBP1 in ovarian tumor progression and elucidate its mechanism of action.
  • To explore the relationship between PCBP1, autophagy, p62/SQSTM1, and apoptosis in ovarian cancer.

Main Methods:

  • Analysis of PCBP1 expression in clinical ovarian tumor samples.
  • Investigated the impact of PCBP1 modulation on autophagy-related gene expression (ULK, ATG12, ATG7, LC3B).
  • Assessed the effect of PCBP1 on p62/SQSTM1 stability and degradation pathways.
  • Examined the correlation between PCBP1, p62/SQSTM1, caspase-8, and patient survival.

Main Results:

  • PCBP1 downregulation is significantly associated with ovarian tumor progression.
  • PCBP1 overexpression attenuates cellular autophagy by affecting key autophagy-related genes.
  • PCBP1 upregulates p62/SQSTM1 by inhibiting its degradation and stabilizing its mRNA.
  • PCBP1 expression correlates with p62/SQSTM1 and caspase-8 levels, impacting overall survival in ovarian cancer patients.

Conclusions:

  • PCBP1 functions as a critical suppressor of ovarian tumor initiation by regulating autophagy and apoptosis.
  • PCBP1 depletion promotes tumorigenesis through enhanced autophagy and altered p62/SQSTM1 levels.
  • Targeting tumor cell autophagy with inhibitors presents a potential therapeutic strategy for PCBP1-deficient ovarian cancers.
Keywords:
PCBP1apoptosisautophagycaspase-8colon cancerovary cancerp62/SQSTM1

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