IGF2BP2-induced circRNF20 facilitates breast cancer cell proliferation via the HuR/CDCA4 axis.

Abstract

This study aimed to explore the mechanism of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) affecting the proliferation of breast cancer (BC) cells. The expression of IGF2BP2, circRNA ring finger protein 20 (circRNF20), and cell division cycle-associated protein 4 (CDCA4) in human BC cells and normal breast epithelial cells was detected via RT-qPCR or Western blotting. After IGF2BP2 expression was altered, CCK-8 assay, colony formation assay, and EdU staining were performed to evaluate changes in the proliferation of BC cells. RNA immunoprecipitation (RIP) assay was used to analyze the binding of circRNF20 to IGF2BP2 or HuR, as well as the binding of HuR to CDCA4. RNA pull-down confirmed the interaction between circRNF20 and HuR. The stability of circRNF20 was tested after treatment with actinomycin D. A nude mouse xenograft tumor model was established to validate the effect of IGF2BP2 in vivo. IGF2BP2, circRNF20, and CDCA4 were highly expressed in BC cells. Silencing IGF2BP2 decreased the proliferation ability of BC cells. Mechanistically, the binding of IGF2BP2 to circRNF20 prevented circRNF20 degradation, thereby promoting the binding of circRNF20 to HuR and increasing the expression of CDCA4. The overexpression of circRNF20 or CDCA4 abolished the inhibitory effect of IGF2BP2 silencing on BC cell proliferation. In conclusion, the binding of IGF2BP2 to circRNF20 prevents its degradation, thus facilitating BC cell proliferation via the HuR/CDCA4 axis.