circHIPK3 nucleates IGF2BP2 and functions as a competing endogenous RNA.

Area of Science:

• Molecular Biology
• Genomics
• Cancer Research

Background:

• Circular RNAs (circRNAs) are key regulators of gene expression implicated in disease pathogenesis.
• circHIPK3 is a novel circRNA with a potential role in cellular regulation.

Purpose of the Study:

• To elucidate the gene-regulatory function of circHIPK3.
• To investigate the interaction between circHIPK3 and RNA binding proteins (RBPs).
• To explore the role of circHIPK3 in bladder cancer.

Main Methods:

• Analysis of large genomics datasets and cell biological experiments.
• Temporal depletion of circHIPK3 and RBPs, followed by RNA sequencing.
• Expression-coupled motif analysis, eCLIP data mining, RNA-immunoprecipitation, and competition assays.

Main Results:

• Identified an 11-mer motif in circHIPK3 that binds IGF2BP2, regulating target mRNAs like STAT3.
• Demonstrated that circHIPK3 sequesters IGF2BP2, potentially via phase separation into condensates, influencing mRNA stabilization.
• Showed circHIPK3 expression correlates with overall survival in bladder cancer patients.

Conclusions:

• circHIPK3 acts as a scaffold to induce IGF2BP2 condensation, regulating key factors for cell proliferation and cancer progression.
• The findings propose a novel regulatory mechanism involving circRNA-mediated protein condensation.
• circHIPK3 holds potential as a biomarker for bladder cancer prognosis.