Identification by comprehensive bioinformatics analysis of KIF15 as a candidate risk gene for triple-negative breast cancer

Abstract

Background: Previous studies have shown that kinesin family proteins (KIFs) play an indispensable roles in several types of cancer. However, the expression and clinical significance of KIFs in triple-negative breast cancer remain unclear. Methods: In this study, the role of KIF15, including gene expression analysis, methylation characteristic, CNV characteristic, and miRNA target regulation, was evaluated using multi-ple bioinformatic tools based on TCGA database. Quantitative real-time PCR and Western blot were used to determine the expression level of KIF15 in triple-negative breast cancer cell lines. Then, functional experiments were employed to explore the effects of KIF15 on tumor growth and metastasis in triple-negative breast cancer. Results: Our data showed that KIF15 was significantly upregulated in triple-negative breast cancer (TNBC). Functionally, downregulation of KIF15 significantly facilitated apoptosis and G2/M phase arrest, and inhibited the migration and invasion of TNBC cells. The mechanism of action of KIF15 was closely related to DNA replication checkpoint and cell cycle regulation in TNBC based on GSEA. In addition, bioinformatics analysis demonstrated that high expression of KIF15 in TNBC was correlated with copy number aberration and DNA methylation levels. Conclusion: Our findings suggest that KIF15 is a novel oncogene in TNBC and provide us a strong evidence that it might be served as a potential clinical target and biomarker in triple-negative breast cancer.