VASP is upregulated by WDR5-MYC nexus and promotes cell migration in breast cancer

Abstract Backguroud: Breast cancer is one of the most threatening diseases for women, whose metastasis and recurrence are important causes of death in breast cancer patients. Vasodilator-stimulated phosphoprotein (VASP) is a cytoskeletal regulatory protein that promotes invasion and metastasis of tumor cells by regulating cell migration. Bioinformatics data indicated that H3K4me3, WDR5 and MYC co-enriched in the VASP promoter region. Aims: The purpose of this study is to demonstrate the regulatory function and mechanism of WDR5-MYC nexus complex on VASP in breast cancer.Method: In this present study, the expression of VASP in breast cancer and adjacent normal tissues was detected by RT-qPCR. The enrichment of H3K4me3, WDR5 and MYC on the VASP promoter was analyzed by ChIPseeker R package and verified by ChIP-PCR. The interaction of H3K4me3, WDR5 and MYC in breast cancer cells was detected by immunoprecipitation and immunofluorescence. Transcriptional activation function of MYC on VASP was detected by site-directed mutagenesis and dual fluorescence reporter system. The regulatory effect of WDR5 on breast cancer cell migration was tested by wund healing and transwell.Result: VASP is up-regulated in breast cancer tissues as compared with adjacent normal tissues. There is interaction between H3K4me3, WDR5 and MYC and co-enrichment on the VASP promoter. MYC can activate VASP transcription by binding to the VASP promoter-842 binding site. WDR5 and MYC can enhance the migration ability of breast cancer cells by up-regulating VASPConclusion: Our results suggest that WDR5-MYC nexus can activate the transcription of VASP by binding to the VASP promoter region, and promote the migration of breast cancer by up-regulating the expression level of VASP.