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PLA2G10 facilitates the cell-cycle progression of soft tissue leiomyosarcoma cells at least by elevating cyclin

Gang Tan1, Guang-Yan Zhang2, Jing Xu3

  • 1Department of Orthopedics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.

Biochemical and Biophysical Research Communications
|May 20, 2020
PubMed

Insights

Phospholipase A2 group 10 (PLA2G10) is identified as a key gene associated with relapse in soft tissue leiomyosarcoma (STLMS). Its overexpression promotes tumor growth by enhancing cell cycle progression, highlighting PLA2G10 as a potential therapeutic target for STLMS.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Soft tissue leiomyosarcoma (STLMS) is a significant subtype of adult sarcoma.
  • Current understanding of STLMS molecular mechanisms is incomplete, lacking identified therapeutic targets.
  • Systematic screening is needed to identify genes associated with STLMS relapse.

Purpose of the Study:

  • To systematically screen for relapse-associated genes in STLMS using TCGA-SARC data.
  • To investigate the functional role of the top-ranking relapse-prediction gene in STLMS.
  • To explore the therapeutic potential of targeting identified genes in STLMS.

Main Methods:

  • Utilized The Cancer Genome Atlas-Sarcoma (TCGA-SARC) database for gene expression analysis.
  • Performed ROC analysis to identify genes with high relapse-prediction value (AUC > 0.80).
  • Conducted in-vitro (cell culture) and in-vivo (xenograft) studies to assess gene function.
  • Investigated the impact of gene overexpression and knockdown on cell growth and cell cycle.
  • Analyzed effects on key cell cycle regulators (e.g., CDK2, cyclin E1).
  • Mutated critical catalytic residues to assess the role of enzymatic activity.

Main Results:

  • AMH and PLA2G10 were identified as significant relapse-associated genes in STLMS.
  • High expression of PLA2G10 correlated with significantly worse relapse-free survival (RFS).
  • PLA2G10 was specifically overexpressed in STLMS compared to other sarcoma subtypes.
  • PLA2G10 overexpression promoted STLMS cell growth and G1/S cell cycle transition.
  • PLA2G10 knockdown inhibited cell growth and induced G1 phase arrest.
  • PLA2G10 increased CDK2 and cyclin E1 expression, crucial for G1/S transition.
  • PLA2G10 overexpression enhanced tumor growth in vivo; inhibition slowed growth.
  • Enzymatic activity of PLA2G10 was essential for its oncogenic properties.

Conclusions:

  • PLA2G10 is a specific relapse-associated gene in soft tissue leiomyosarcoma.
  • PLA2G10 promotes STLMS cell-cycle progression, at least by upregulating cyclin E1 and CDK2.
  • The hydrolytic activity of PLA2G10 is critical for its oncogenic function, suggesting it as a potential therapeutic target.
Keywords:
CDK2Cell-cycleCyclin E1PLA2G10Soft tissue leiomyosarcoma

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