CircATP5C1 promotes triple-negative breast cancer progression by binding IGF2BP2 to modulate CSF-1 secretion

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Triple-negative breast cancer (TNBC) poses a significant global health threat.
• Circular RNAs (circRNAs) are increasingly recognized for their roles in human cancers, including TNBC.
• The specific mechanisms of most circRNAs in TNBC progression remain largely unknown.

Purpose of the Study:

• To investigate the function and mechanism of a novel circRNA, circATP5C1, in triple-negative breast cancer.
• To determine if circATP5C1 expression correlates with TNBC patient prognosis.
• To elucidate the molecular pathway through which circATP5C1 influences TNBC progression.

Main Methods:

• Tissue microarray analysis to correlate circATP5C1 expression with TNBC patient prognosis.
• Gain- and loss-of-function experiments in TNBC cell lines to assess circATP5C1's biological functions.
• RNA sequencing, RNA pull-down assays, mass spectrometry, RNA FISH-immunofluorescence, and RNA immunoprecipitation (RIP) to identify and validate molecular interactions and targets.

Main Results:

• CircATP5C1 expression was found to be a predictive factor for TNBC patient prognosis.
• CircATP5C1 significantly promoted the progression of TNBC cells in vitro.
• Mechanistically, circATP5C1 binds to IGF2BP2, leading to increased secretion of Colony stimulating factor 1 (CSF-1), thereby accelerating TNBC progression.

Conclusions:

• CircATP5C1 serves as a novel prognostic biomarker for triple-negative breast cancer.
• The circATP5C1/IGF2BP2/CSF-1 axis represents a newly identified pathway driving TNBC progression.
• Targeting this pathway may offer potential therapeutic strategies for TNBC.