A circular RNA molecules: the prognosis of breast cancer sentry

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Abstract

Background

Increasing 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.
Methods
They 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. They investigated the regulatory effect of circKIF4A on miRNA and its target genes to explore the potential regulatory mechanisms of circKIF4A in TNBC.

(Fig from.Molecular Cancer)

Results
qRT-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.

Conclusions
The 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.

Background
Circular RNAs (circRNAs) have multiple functions, including miRNA binding, protein binding, regulation of protein translation. CircRNAs can act as oncogenes or tumor suppressors, therefore, they could be used as biomarkers or therapeutic targets for cancer. But the role of circRNAs in triple-negative breast cancer (TNBC) remains unclear.

RNAs can serve as competitive endogenous RNAs (ceRNAs) and compete for shared microRNAs (miRNAs) . circRNAs have advantages as ceRNAs, as they have no free ends, predominant localization in the cytoplasm and a largely noncoding nature. With miRNA-binding sites, circRNAs could function as miRNA sponges, which would lead to loss of miRNA function and which would be accompanied by increased gene targets. Memczak S et al. found that the circRNA CDR1as was a negative regulator of miR-7 . In cancers, the circRNA CCDC66 has been shown to sponge miRNAs that target oncogenes, which promote cancer growth and metastasis. Moreover, circPVT1 also sponges several tumor suppressor miRNAs including let-7b. These findings have urged us to explore the use of circRNAs as therapeutic targets.

Here, They reanalyzed the circRNA expression microarray that THEY did in our previous study . The top upregulated circRNA termed circKIF4A was confirmed significantly upregulated and positively associated with a worse outcome in TNBC. A series of in vitro and in vivo experiments was performed to explore the function of circKIF4A in TNBC progression. They found that circKIF4A could regulate TNBC cell proliferation and migration. Then They explored the potential regulatory mechanisms of circKIF4A in TNBC and found that circKIF4A regulated the expression of KIF4A via sponging miR-375 to exert its regulatory functions in TNBC. The circKIF4A-miR-375-KIF4A axis regulates TNBC progression via the ceRNA mechanism. Therefore, circKIF4A may act as a prognostic biomarker and therapeutic target for TNBC.

Read more,please click : https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0946-x

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