Abstract:
Background: Nucleoporins (Nups) constitute a large group of proteins that are structurallyarranged at the nuclear envelope and facilitate the bidirectional movement of molecules acrossthe nuclear membrane. In addition to regulating the shuttling of ribonucleoprotein complexes,RNAs and proteins, various Nups interact with chromatin either directly or indirectly, thus regulatinggene expression. Any mutations or expression anomalies of Nups may lead to abnormal localization ofcritical molecules, or dysregulated expression of genes that they interact with. A comprehensivegenomic 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 GenomeAtlas), Genotype-Tissue Expression (GTEx) and microarray platforms and conducted in silico analysis ofall the genes encoding nucleoporins that are associated with the Nuclear Pore Complexes (NPCs). Formutation detection, we used cBioportal; for expression analysis, we used Xena and for patient survivalplots, KMPlot was utilized.Results: The genetic and molecular profile of nucleoporin genes identified multiple mutations anddetected aberrant expression in breast cancer. Interestingly, NUP133, AHCTF1, TPR, Nup121L showedsimultaneous gene amplification in nearly 10% of breast cancer patients. In addition, deregulatedexpression 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 geneticprofile of nucleoporins genes in breast cancer and underscores the critical roles of various nucleoporinsin cancer progression. The identified molecules may advance our understanding of the etiology of thedisease and serve as possible targets for novel therapeutic strategies in cancer.
Page(s):
98-110
DOI:
DOI not available
Published:
Journal: Advancements in life sciences, Volume: 9, Issue: 1, Year: 2022
Keywords:
Breast cancer
,
bioinformatics
,
Nucleoporins
,
Nuclear Pore Complexes NPCs