FAM72A Knockdown Drives Cell Mitophagy and Pyroptosis in Ovarian Cancer Via the PINK1/Parkin Pathway

Songhong Tan1, Li Wang2, Zhengmei Xu1

  • 1Department of Gynecology, Affiliated Hengyang Hospital of Hunan Normal University & Hengyang Central Hospital, No. 31 Guanghui Road, Zhengxiang District, Hengyang City, Hunan, 421000, China.

Insights

Family with Sequence Similarity 72 Member A (FAM72A) promotes ovarian cancer (OC) growth by inhibiting mitophagy and pyroptosis. Silencing FAM72A activates the PINK1/Parkin pathway, driving these processes and offering a potential therapeutic strategy for OC.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Ovarian cancer (OC) remains a leading cause of cancer-related deaths.
  • Understanding novel molecular mechanisms regulating OC progression is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of Family with Sequence Similarity 72 Member A (FAM72A) in regulating mitophagy and pyroptosis in ovarian cancer.
  • To elucidate the involvement of the PINK1/Parkin pathway in FAM72A-mediated OC progression.

Main Methods:

  • Bioinformatics analysis, clinical tissue and cell assays, and in vivo experiments were employed.
  • FAM72A expression and its effects on cell proliferation, invasion, migration, apoptosis, mitophagy, and pyroptosis were assessed.
  • The involvement of the PINK1/Parkin pathway was investigated through gene silencing and pharmacological inhibition.

Main Results:

  • FAM72A was significantly overexpressed in OC tissues and cell lines.
  • FAM72A knockdown suppressed OC cell proliferation, invasion, and migration, while promoting apoptosis.
  • FAM72A downregulation activated the PINK1/Parkin pathway, leading to enhanced mitophagy and pyroptosis, evidenced by increased mitochondrial ROS, autophagosome-mitochondria colocalization, LC3II/I ratio, and pyroptosis markers (NLRP3, ASC, cleaved caspase-1, IL-1β, IL-18), and decreased p62, mitochondrial membrane potential, and ATP levels.
  • Inhibition of the PINK1/Parkin pathway reversed the anti-tumor effects of FAM72A knockdown.

Conclusions:

  • FAM72A promotes ovarian cancer progression by suppressing mitophagy and pyroptosis through the inhibition of the PINK1/Parkin pathway.
  • FAM72A knockdown induces mitophagy and pyroptosis by activating the PINK1/Parkin pathway, suggesting FAM72A as a potential therapeutic target for ovarian cancer.

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