circKIF4A acts as a prognostic factor and mediator to regulate the progression of triple-negative breast cancer.

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:

We 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.

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.

• Authors: Hailin Tang, Xiaojia Huang, Jin Wang, Lu Yang, Yanan Kong, Guanfeng Gao, Lijuan Zhang, Zhe-Sheng Chen, Xiaoming Xie
• Journal: Molecular cancer (Mol Cancer) Vol. 18 Issue 1 Pg. 23 (02 11 2019) ISSN: 1476-4598 [Electronic] England
• PMID: 30744636 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN375 microRNA, human
• MicroRNAs
• RNA, Circular
• RNA, Small Interfering
• RNA
• KIF4A protein, human
• Kinesins

Topics

• Adult
• Aged
• Animals
• Cell Line, Tumor
• Cell Proliferation
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Kinesins (genetics, metabolism)
• Lung Neoplasms (diagnosis, genetics, mortality, secondary)
• MCF-7 Cells
• Mice
• Mice, Inbred BALB C
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Neoplasm Staging
• Prognosis
• RNA (antagonists & inhibitors, genetics, metabolism)
• RNA, Circular
• RNA, Small Interfering (genetics, metabolism)
• Signal Transduction
• Survival Analysis
• Triple Negative Breast Neoplasms (diagnosis, genetics, mortality, pathology)
• Xenograft Model Antitumor Assays