Abstract
Background: Nucleoporins (Nups) constitute a large group of proteins that are structurally arranged at the nuclear envelope and facilitate the bidirectional movement of molecules across the nuclear membrane. In addition to regulating the shuttling of ribonucleoprotein complexes, RNAs and proteins, various Nups interact with chromatin either directly or indirectly, thus regulating gene expression. Any mutations or expression anomalies of Nups may lead to abnormal localization of critical molecules, or dysregulated expression of genes that they interact with. A comprehensive genomic study encompassing all Nup genes in relation to breast cancer is lacking. Methods: We used genomic and transcriptomic datasets from Pan-Cancer TCGA (The Cancer Genome Atlas), Genotype-Tissue Expression (GTEx) and microarray platforms and conducted in silico analysis of all the genes encoding nucleoporins that are associated with the Nuclear Pore Complexes (NPCs). For mutation detection, we used cBioportal; for expression analysis, we used Xena and for patient survival plots, KMPlot was utilized. Results: The genetic and molecular profile of nucleoporin genes identified multiple mutations and detected aberrant expression in breast cancer. Interestingly, NUP133, AHCTF1, TPR, Nup121L showed simultaneous gene amplification in nearly 10% of breast cancer patients. In addition, deregulated expression of some of the nucleoporins, namely, NUP62, NUP 93, NUP98, NUP155, POM121L12, RAE1, SEC13, TPR were correlated with patient prognosis. Conclusion: The current study is the first one that unravels a comprehensive molecular and genetic profile of nucleoporins genes in breast cancer and underscores the critical roles of various nucleoporins in cancer progression. The identified molecules may advance our understanding of the etiology of the disease and serve as possible targets for novel therapeutic strategies in cancer.