Molecular profiling of nucleocytoplasmic transport factor genes in breast cancer

Abstract

Transport of functional molecules across the nuclear membrane of a eukaryotic cell is regulated by a dedicated set of transporter proteins that carry molecules into the nucleus or out of the nucleus to the cytoplasm for homeostasis of the cell. One of the categories of cargo molecules these transporters carry are the molecules for cell cycle regulation. Therefore, their role is critical in terms of cancer development. Any misregulation of the transport factors would means aberrant abundance of cell cycle regulators and might have consequences in cell cycle progression. While earlier studies have focussed on individual transport related molecules, a collective overview of how these molecules may be dysregulated in breast cancer is lacking.

Using genomic and transcriptomic datasets from TCGA (The Cancer Genome Atlas) and microarray platforms, we carried out bioinformatic analysis and provide a genetic and molecular profile of all the molecules directly related to nucleocytoplasmic shuttling of proteins and RNAs. Interestingly, we identified that many of these molecules are either mutated or have dysregulated expression in breast cancer. Strikingly, some of the molecules, namely, KPNA2, KPNA3, KPNA5, IPO8, TNPO1, XPOT, XPO7 and CSE1L were correlated with poor patient survival. This study provides a comprehensive genetic and molecular landscape of nucleocytoplasmic factors in breast cancer and points to the important roles of various nucleocytoplasmic factors in cancer progression. This data might have implications in prognosis and therapeutic targeting in breast cancer.

Abstract

Nuclear transport; Breast cancer; Genetic profile