circAGFG1 Facilitates the Progression of Non-Triple-Negative Breast Cancer Through miR-143-5p/USP14 Axis

Abstract

Circular RNAs (circRNAs) emerged as a new class of regulators in various human diseases, including breast cancer (BC). Our previous study identified that circAGFG1 could promote triple-negative breast cancer (TNBC) progression. However, the clinical values and functions of circAGFG1 in non-TNBC remain elusive. Here, we applied qRT-PCR in 30 pairs of non-TNBC tissues and para-cancerous tissues and in situ hybridization (ISH) in 346 paraffin-embedded non-TNBC tissues to evaluate the expression pattern and clinical significance of circAGFG1 in non-TNBC. Gain- and loss-of-function studies were carried out to determine the biological function of circAGFG1 in non-TNBC in vitro and in vivo. Mechanistically, RNA pull-down, RNA immunoprecipitation, dual luciferase reporter, fluorescent in situ hybridization assays were employed to validate the interaction between circAGFG1 and miR-143-5p as well as miR-143-5p and USP14. We found that circAGFG1 was markedly increased in non-TNBC tissues as well. Moreover, patient suffering from non-TNBC with a higher expression level of circAGFG1 presents a worse clinical outcome. Multivariate analysis uncovered that high level of circAGFG1 might serve as a standalone risk factor for non-TNBC patients. Functional studies substantiated that enforced expression of circAGFG1 increased the malignance of non-TNBC cells, whereas silencing of circAGFG1 produced the opposite. Mechanistic investigations proved that circAGFG1 sponged miR-143-5p to regulate the level of oncogene USP14, leading to the progression of non-TNBC. Taken together, our data revealed that circAGFG1 could also accelerate the progression of non-TNBC via miR-143-5p/USP14 axis and might provide an alternative target for the diagnosis and treatment of non-TNBC.