EMX2OS targeting IGF2BP1 represses Wilms' tumour stemness,epithelial-mesenchymal transition and metastasis

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Wilms' tumour (WT) is a common pediatric renal malignancy with poor outcomes.
• Identifying novel therapeutic targets is crucial for improving WT treatment.
• The role of long non-coding RNAs (lncRNAs) in WT pathogenesis is increasingly recognized.

Purpose of the Study:

• To investigate the role of lncRNA EMX2 opposite strand/antisense RNA (EMX2OS) in Wilms' tumour (WT).
• To elucidate the interaction between EMX2OS and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in WT cells.
• To determine the impact of EMX2OS on WT cell stemness, epithelial-mesenchymal transition (EMT), and metastasis.

Main Methods:

• Real-time quantitative polymerase chain reaction (RT-qPCR) for gene expression analysis.
• Sphere formation, scratch, and transwell assays to assess stemness, migration, and invasion.
• Western blotting for EMT-related protein detection.
• RNA pull down and RIP assays to confirm RNA-protein interactions.
• In vivo xenograft tumour assays to evaluate tumorigenicity.

Main Results:

• EMX2OS was downregulated, while IGF2BP1 was upregulated in WT tissues.
• EMX2OS overexpression or IGF2BP1 knockdown inhibited WT cell stemness, migration, invasion, and EMT.
• EMX2OS directly interacted with IGF2BP1.
• IGF2BP1 overexpression reversed the suppressive effects of EMX2OS.
• EMX2OS inhibited in vivo tumour growth, stemness, and EMT via IGF2BP1.

Conclusions:

• EMX2OS functions as a tumour suppressor in Wilms' tumour.
• EMX2OS inhibits WT cell stemness, EMT, and metastasis by interacting with IGF2BP1.
• The EMX2OS-IGF2BP1 axis represents a potential novel therapeutic target for WT.