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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
Summary
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).
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.
