Abstract
Previous data show that the knockdown of the MYBL1 gene in the MDA-MB-231 cell line leads to the downregulation of VCPIP1 gene expression. In addition, MYBL1 and VCPIP1 genes are co-expressed and dysregulated in some of the same triple negative breast cancer patient samples. We propose that the co-expression of the two genes is attributed to the MYBL1 transcription factor regulation of the VCPIP1 gene. We identify the MYBL1 transcription factor binding site upstream of the VCPIP1 start site and show that the MYBL1 protein can bind to the sequence identified in the VCPIP1 promoter region. Combined with the results from the knockdown study, these data support the ability of MYBL1 to regulate the VCPIP1 gene. The VCPIP1 gene functions as a deubiquitinating enzyme involved in DNA repair, protein positioning, and the assembly of the Golgi apparatus during mitotic signaling. The transcriptional regulation of VCPIP1 by the MYBL1 gene could implicate MYBL1 in these processes, which might contribute to tumor processes in TNBC. Although both genes are involved in cell cycle regulatory mechanisms, converging signaling mechanisms have not been identified. In a separate study, we performed sequence alignment of the MYBL1 transcript variants and identified an exon unique to the canonical variant. Probes that specifically target the unique MYBL1 exon show that the exon is overexpressed in tumor cell lines compared to non-tumor breast cells. We are classifying this unique MYBL1 exon as a tumor-associated exon.