Abstract
The gene RAE1 encodes ribonucleic acid export 1 (RAE1), which is involved in mRNA export and is known to serve as a mitotic checkpoint regulator. In addition, RAE1 haplo-insufficiency leads to chromosome missegregation and early aging-associated phenotypes. In humans, a positive correlation has been found between RAE1 copy number abnormalities and gene amplification in breast cancer cells. However, the precise functional role of RAE1 in breast cancer remains to be determined. An in silico analysis of data retrieved from GENT and cBio-Portal identified RAE1 upregulation in breast cancer tissues relative to normal breast cells. Functional studies of various cell lines showed that RAE1 induced invasive and migratory abilities by regulating epithelial-mesenchymal transition signals. A tissue microarray was constructed to demonstrate the interrelationship between clinicopathological features and RAE1 expression. Immunohistochemistry revealed a positive correlation between RAE1 expression and a high histologic grade. Furthermore, RAE1 overexpression was associated with considerably poorer disease-free survival and distant metastasis-free survival, especially in patients with oestrogen receptor-positive tumours. In summary, RAE1 may be a prognostic marker and therapeutic intervention target in malignant breast cancers.
Highlights
Ribonucleic acid export 1 (Rae1) was originally discovered as an essential nucleocytoplasmic transport factor in yeast, and is known to be involved in the export of nuclear mRNA to the cytoplasm[1]
Our integration of in silico resources confirmed the overexpression of ribonucleic acid export 1 (RAE1) in patients with breast cancer, in accordance with previous reports that demonstrated RAE1 copy number variation (CNV) and gene expression abnormalities[14,15]
Namely the correlations of RAE1 overexpression with a high histologic grade and poor prognosis and identification of a functional role of RAE1 in cancer cell migration and invasion, strongly support the notion that RAE1 contributes to breast cancer progression
Summary
Ribonucleic acid export 1 (Rae1) was originally discovered as an essential nucleocytoplasmic transport factor in yeast, and is known to be involved in the export of nuclear mRNA to the cytoplasm[1]. The shuttling of human RAE1 between the nucleus and cytoplasm and the ability of RAE1 to form complexes with nuclear pore proteins suggest a role for RAE1 in mRNA export in humans[5]. These results demonstrate a critical role for mammalian RAE1 as a nuclear exporter of mRNA and/or mitotic checkpoint regulator to ensure the maintenance of proper spindle bipolarity[3,5,6]. RAE1 is associated with genome amplification and copy-number driven expression and has been proposed as a putative oncogene[14]. A combined tissue microarray (TMA) and survival analysis revealed the prognostic significance of RAE1 and a positive correlation between RAE1 expression and histologic grade in invasive ductal carcinomas
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