Diagnostic and Prognostic Profiling of Nucleocytoplasmic Shuttling Genes in Hepatocellular Carcinoma

Abstract

One of the key features of eukaryotic cells is the separation of nuclear and cytoplasmic compartments by a double-layer nuclear envelope. This separation is crucial for timely regulation of gene expression, mRNA biogenesis, cell cycle, and differentiation. Since transcription takes place in the nucleus and the major part of translation in the cytoplasm, proper distribution of biomolecules between these two compartments is ensured by nucleocytoplasmic shuttling proteins – karyopherins. Karyopherins transport biomolecules through nuclear pores bidirectionally in collaboration with Ran GTPases and utilize GTP as the source of energy. Different karyopherins transport different cargo molecules that play important roles in the regulation of cell physiology. In cancer cells, this nucleocytoplasmic transport is significantly dysregulated to support increased demands for the import of cell cycle-promoting biomolecules and export of cell cycle inhibitors and mRNAs. Here, we analysed genomic, transcriptomic and proteomic data from published datasets to comprehensively profile karyopherin genes in hepatocellular carcinoma. We have found out that expression of multiple karyopherin genes is increased in hepatocellular carcinoma in comparison to the normal liver, with importin subunit α-1, exportin 2, importin subunit β-1 and importin 9 being the most over-expressed. More­over, we have found that increased expression of these genes is associated with higher neoplasm grade as well as significantly worse overall survival of liver cancer patients. Taken together, our bioinformatic data-mining analysis provides a comprehensive geno­mic and transcriptomic landscape of karyopherins in hepatocellular carcinoma and identifies potential members that could be targeted in order to develop new treatment regimens.