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

Abstract

Triple-negative breast cancer (TNBC) is a common malignant disease among females and severely threatens the health of women worldwide. Nowadays, circular RNAs (circRNAs) aroused our interest for their functions in human cancers, including TNBC. However, the mechanism of most circRNAs in the progression of TNBC remains unclear. We found a novel circRNA named circATP5C1, whose function in TNBC remains uncovered. Tissue microarray was used to analyze the association between the expression of circATP5C1 and the prognoses of TNBC patients. Gain-and loss-of-function experiments were performed to validate the biological functions of circATP5C1 in different TNBC cell lines. RNA-seq analyses were conducted to find out the target genes regulated by circATP5C1. RNA pull-down assay and mass spectrometry were used to select the proteins associated with circATP5C1. RNA FISH-immunofluorescence and RNA immunoprecipitation (RIP) were complemented to validate the interaction between circATP5C1 and its binding protein. CircATP5C1 was identified to have predictive function in prognosis of TNBC patients. CircATP5C1 advanced the progression of TNBC cells. Mechanistically, Colony stimulating factor 1 (CSF-1) is a vital downstream gene regulated by circATP5C1. The alteration of CSF-1 expression level was validated due to the interaction between circATP5C1 and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2). Rescue experiments demonstrated that circATP5C1 accelerates the progression of TNBC partly via binding with IGF2BP2 to increase the secretion of CSF-1. This study uncovers a novel mechanism of circATP5C1/IGF2BP2/CSF-1 pathway in regulating progression of TNBC.