Department of Anatomy, Embryology Laboratory, and Brain Korea 21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.
Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang 10444, Korea.
Sci Rep. 2017 Feb 9;7:42256. doi: 10.1038/srep42256.
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.
基因 RAE1 编码 RNA 输出 1（RAE1），它参与 mRNA 输出，已知作为有丝分裂检查点调节剂。此外，RAE1 单倍体不足导致染色体错误分离和与衰老相关的表型。在人类中，已经发现 RAE1 拷贝数异常与乳腺癌细胞中的基因扩增之间存在正相关。然而，RAE1 在乳腺癌中的精确功能作用仍有待确定。从 GENT 和 cBio-Portal 检索到的数据的计算机分析表明，RAE1 在乳腺癌组织中相对于正常乳腺细胞上调。对各种细胞系的功能研究表明，RAE1 通过调节上皮-间充质转化信号诱导侵袭和迁移能力。构建组织微阵列以证明 RAE1 表达与临床病理特征之间的相互关系。免疫组织化学显示 RAE1 表达与高组织学分级之间存在正相关。此外，RAE1 过表达与疾病无进展生存和远处无转移生存显著相关，尤其是在雌激素受体阳性肿瘤患者中。总之，RAE1 可能是恶性乳腺癌的预后标志物和治疗干预靶点。
