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Abstract
BackgroundIncreasing studies has found that circular RNAs (circRNAs) play vital roles in cancer progression. But the expression profile and function of circRNAs in triple-negative breast cancer (TNBC) are unclear.MethodsWe used a circRNA microarray to explore the circRNA expression profile of TNBC. The expression of the top upregulated circRNA, circKIF4A, was confirmed by qRT-PCR in breast cancer cell lines and tissues. Kaplan-Meier survival analysis was conducted to analyze the clinical impact of circKIF4A on TNBC. A series of experiments was performed to explore the functions of circKIF4A in TNBC progression, such as cell proliferation and migration. We investigated the regulatory effect of circKIF4A on miRNA and its target genes to explore the potential regulatory mechanisms of circKIF4A in TNBC.ResultsqRT-PCR analyses verified that circKIF4A was significantly upregulated and positively associated with poorer survival of TNBC. The inhibition of circKIF4A suppressed cell proliferation and migration in TNBC. Luciferase reporter assay and RNA immunoprecipitation assay revealed that circKIF4A and KIF4A could bind to miR-375 and that circKIF4A regulated the expression of KIF4A via sponging miR-375.ConclusionsThe circKIF4A-miR-375-KIF4A axis regulates TNBC progression via the competitive endogenous RNA (ceRNA) mechanism. circKIF4A may therefore serve as a prognostic biomarker and therapeutic target for TNBC.
Highlights
Increasing studies has found that circular RNAs play vital roles in cancer progression
We explored the potential regulatory mechanisms of circKIF4A in triple-negative breast cancer (TNBC) and found that circKIF4A regulated the expression of KIF4A via sponging miR-375 to exert its regulatory functions in TNBC
Results circKIF4A is upregulated and correlated with poor clinical outcomes of TNBC To explore the circRNA expression profile of TNBC, we reanalyzed the circRNA microarray we did in our previous study [7]
Summary
Increasing studies has found that circular RNAs (circRNAs) play vital roles in cancer progression. The expression profile and function of circRNAs in triple-negative breast cancer (TNBC) are unclear. Circular RNAs (circRNAs) have multiple functions, including miRNA binding, protein binding, regulation of protein translation [1]. CircRNAs can act as oncogenes or tumor suppressors, they could be used as biomarkers or therapeutic targets for cancer. The role of circRNAs in triple-negative breast cancer (TNBC) remains unclear. CircRNAs have advantages as ceRNAs, as they have no. We reanalyzed the circRNA expression microarray that we did in our previous study [7]. The top upregulated circRNA termed circKIF4A was confirmed significantly upregulated and positively associated with a worse outcome in TNBC.
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