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PLCD1-Induced DNA Damage Inhibits the Tumor Growth via Downregulating CDKs in Chondrosarcoma

Jiakang Shen1,2, Chen Yu1,3, Zhuoying Wang2

  • 1Shanghai General Hospital of Nanjing Medical University, Shanghai, China.

Journal of Oncology
|July 15, 2022
PubMed
Abstract

Insights

Phospholipase C delta 1 (PLCD1) is downregulated in high-grade chondrosarcoma. Overexpressing PLCD1 induces DNA damage, halting cell cycle and promoting apoptosis, offering a potential therapeutic target for chondrosarcoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • High-grade chondrosarcoma lacks specific diagnostic and therapeutic genes.
  • Understanding novel gene functions is crucial for developing targeted treatments.

Purpose of the Study:

  • To investigate the role of Phospholipase C delta 1 (PLCD1) in high-grade chondrosarcoma.
  • To evaluate PLCD1 as a potential therapeutic target for chondrosarcoma.

Main Methods:

  • Analyzed PLCD1 expression in 49 patients and compared with TCGA database.
  • Generated PLCD1 knockdown and overexpression cell lines.
  • Assessed cell proliferation, cell cycle, and apoptosis.
  • Utilized Western blotting and established animal xenografts.

Main Results:

  • PLCD1 expression inversely correlates with chondrosarcoma grade, being lower in high-grade tumors.
  • PLCD1 overexpression suppressed cell cycle regulators (CDKs/cyclins) and induced DNA damage.
  • In vitro and in vivo studies confirmed PLCD1's antitumor effects, including cell cycle arrest and apoptosis.

Conclusions:

  • Reduced PLCD1 expression is characteristic of high-grade chondrosarcoma.
  • PLCD1 acts as a tumor suppressor by inducing DNA damage, cell cycle arrest, and apoptosis.
  • PLCD1 represents a promising novel therapeutic target for high-grade chondrosarcoma drug development.

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