miR-378c suppresses Wilms tumor development via negatively regulating CAMKK2

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Wilms tumor is a pediatric kidney cancer.
• MicroRNAs (miRNAs) are increasingly recognized for their role in Wilms tumor pathogenesis.
• Understanding specific miRNA functions, like miR-378c, is vital for novel therapeutic development.

Purpose of the Study:

• To investigate the expression and functional role of miR-378c in Wilms tumor.
• To identify the molecular targets and mechanisms underlying miR-378c's function in Wilms tumor.

Main Methods:

• Quantitative real-time PCR (qRT-PCR) for miRNA and gene expression analysis.
• In vitro assays (CCK-8, wound healing, Transwell) to assess cell proliferation and metastasis.
• In vivo xenograft assays to evaluate tumor growth inhibition.
• Luciferase reporter assays to confirm direct target interaction.
• Western blot analysis for protein expression.
• Rescue experiments to validate functional relationships.

Main Results:

• miR-378c was significantly downregulated in Wilms tumor tissues and cell lines.
• Overexpression of miR-378c suppressed Wilms tumor cell proliferation and metastasis in vitro and inhibited tumor growth in vivo.
• miR-378c was confirmed to directly target CAMKK2.
• CAMKK2 was highly expressed in Wilms tumor and its expression correlated with enhanced malignancy.
• Restoring miR-378c levels inhibited metastasis by downregulating CAMKK2, while inhibiting miR-378c promoted malignancy, which was reversible by CAMKK2 knockdown.

Conclusions:

• miR-378c acts as a tumor suppressor in Wilms tumor.
• The miR-378c/CAMKK2 axis is a critical regulator of Wilms tumor development and metastasis.
• Targeting the miR-378c pathway presents a promising therapeutic strategy for Wilms tumor.