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NGF/TRKA Decrease miR-145-5p Levels in Epithelial Ovarian Cancer Cells.

Maritza P Garrido1,2, Ignacio Torres1, Alba Avila3

  • 1Laboratorio de Endocrinología y Biología de la Reproducción, Hospital Clínico Universidad de Chile, Santiago 8380456, Chile.

International Journal of Molecular Sciences
|October 21, 2020
PubMed
Summary
This summary is machine-generated.

Nerve Growth Factor (NGF) signaling in ovarian cancer reduces miR-145 levels, hindering tumor suppression. Restoring miR-145 levels inhibits cancer cell growth, invasion, and metastasis, suggesting a potential therapeutic strategy for epithelial ovarian cancer (EOC).

Keywords:
NGFTRKAVEGFc-MYCepithelial ovarian cancermicroRNA-145

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Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Nerve Growth Factor (NGF) and its receptor tropomyosin receptor kinase A (TRKA) are upregulated in epithelial ovarian cancer (EOC).
  • NGF/TRKA signaling promotes EOC progression by increasing oncogenic proteins like c-MYC and VEGF.
  • MicroRNAs (miRs), such as miR-145, regulate gene expression and are often dysregulated in cancer.

Purpose of the Study:

  • To investigate if NGF/TRKA signaling decreases miR-145 levels in EOC cells.
  • To determine the effects of miR-145 upregulation on EOC cell behavior and tumor progression.
  • To explore the therapeutic potential of miR-145 in EOC.

Main Methods:

  • Quantitative PCR (qPCR) to assess miR-145-5p levels in ovarian biopsies and cell lines (HOSE, A2780, SKOV3) stimulated with NGF.
  • Overexpression of miR-145 in ovarian cancer cells to evaluate proliferation, migration, and invasion.
  • Assessment of c-MYC and VEGF protein levels.
  • In vivo studies using mouse models to evaluate tumor formation and metastasis.

Main Results:

  • miR-145-5p levels were significantly lower in EOC samples compared to normal ovarian tissue.
  • NGF stimulation reduced miR-145-5p transcription and abundance in ovarian cell lines.
  • Overexpression of miR-145 inhibited EOC cell proliferation, migration, and invasion.
  • miR-145 upregulation led to decreased c-MYC and VEGF protein levels.
  • In vivo, miR-145 overexpression suppressed tumor formation and metastasis in mice.

Conclusions:

  • NGF/TRKA signaling in EOC is associated with decreased miR-145-5p levels.
  • miR-145-5p plays a crucial role in suppressing EOC cell proliferation, invasion, and metastasis.
  • Upregulation of miR-145-5p represents a promising therapeutic strategy for epithelial ovarian cancer.