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STAT3 regulates miR93-mediated apoptosis through inhibiting DAPK1 in renal cell carcinoma

Yang Du1, Chuize Kong2

  • 1Department of Urology, First Hospital of China Medical University, 110001, Shenyang, China.

Cancer Gene Therapy
|November 24, 2020
PubMed

Insights

Signal transducer and activator of transcription 3 (STAT3) promotes renal cell carcinoma (RCC) by upregulating miR-93, which inhibits DAPK1. This STAT3-miR93-DAPK1 pathway offers a potential therapeutic target for RCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Signal transducer and activator of transcription 3 (STAT3) is crucial in regulating inflammatory responses, cell survival, proliferation, and angiogenesis.
  • Aberrant STAT3 activation is implicated in various cancers, including renal cell carcinoma (RCC).
  • STAT3 signaling pathways are complex and involve multiple feedback loops.

Purpose of the Study:

  • To investigate the role of miR-93-3p in renal cell carcinoma (RCC).
  • To elucidate the regulatory relationship between STAT3, miR-93, and death-associated protein kinase 1 (DAPK1) in RCC.
  • To identify a potential therapeutic pathway for RCC.

Main Methods:

  • Investigated the function of miR-93-3p in RCC cell proliferation and apoptosis.
  • Analyzed the transcriptional regulation of miR-93 by STAT3.
  • Examined the inhibitory effect of miR-93 on DAPK1 expression.
  • Assessed the impact of DAPK1 on STAT3 nuclear translocation.

Main Results:

  • miR-93-3p enhances RCC cell proliferation and suppresses apoptosis, indicating an oncogenic role.
  • STAT3 directly regulates miR-93 transcription.
  • miR-93 inhibits DAPK1 protein expression, and STAT3 further suppresses DAPK1 at the RNA level.
  • Overexpressed DAPK1 inhibits activated STAT3 nuclear entry.

Conclusions:

  • A novel STAT3-miR93-DAPK1 signaling pathway was identified in RCC.
  • This pathway is continuously activated and contributes to RCC progression.
  • The STAT3-miR93-DAPK1 axis represents a potential therapeutic target for RCC treatment.

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