YWHAE gene is located on chromosome 17p13.3, and its product 14-3-3epsilon protein belongs to 14-3-3 protein family. As a molecular scaffold, YWHAE participates in biological processes such as cell adhesion, cell cycle regulation, signal transduction and malignant transformation, and is closely related to many diseases. Overexpression of YWHAE in breast cancer can increase the ability of proliferation, migration and invasion of breast cancer cells. In gastric cancer, YWHAE acts as a negative regulator of MYC and CDC25B, which reduces their expression and inhibits the proliferation, migration, and invasion of gastric cancer cells, and enhances YWHAE-mediated transactivation of NF-κB through CagA. In colorectal cancer, YWHAE lncRNA, as a sponge molecule of miR-323a-3p and miR-532-5p, can compete for endogenous RNA through direct interaction with miR-323a-3p and miR-532-5p, thus up-regulating K-RAS/ERK/1/2 and PI3K-AKT signaling pathways and promoting the cell cycle progression of the colorectal cancer. YWHAE not only mediates tumorigenesis as a competitive endogenous RNA, but also affects gene expression through chromosome variation. For example, the FAM22B-YWHAE fusion gene caused by t(10; 17) (q22; p13) may be associated with the development of endometrial stromal sarcoma. At the same time, the fusion transcript of YWHAE and NUTM2B/E may also lead to the occurrence of endometrial stromal sarcoma. To understand the relationship between YWHAE, NUTM2A, and NUTM2B gene rearrangement/fusion and malignant tumor, YWHAE-FAM22 fusion gene/translocation and tumor, YWHAE gene polymorphism and mental illness, as well as the relationship between 17p13.3 region change and disease occurrence. It provides new idea and basis for understanding the effect of YWHAE gene molecular mechanism and genetic variation on the disease progression, and for the targeted for the diseases.
YWHAE基因位于染色体17p13.3，该基因产物14-3-3epsilon蛋白属于14-3-3蛋白家族。YWHAE作为一个分子支架，参与细胞黏附、细胞周期调节、信号转导和恶性转化等生物学过程，与众多疾病都有着密切关系。在乳腺癌中YWHAE过表达可增加乳腺癌细胞增殖、迁移和侵袭能力；在胃癌中，YWHAE作为MYC和CDC25B的负调控因子，降低两者表达从而抑制胃癌细胞的增殖、迁移和侵袭，并且通过CagA增强YWHAE介导的NF-κB的反式激活；在结直肠癌中，YWHAE lncRNA可以作为miR-323a-3p和miR-532-5p的海绵分子，通过与miR-323a-3p和miR-532-5p的直接相互作用起到竞争内源RNA的作用，从而上调K-RAS/ERK/1/2以及PI3K-AKT信号通路，促进结直肠癌的细胞周期进程。YWHAE除了通过作为竞争内源RNA的方式介导肿瘤的发生，也能通过染色体变异影响基因表达。例如由t(10; 17)(q22; p13)引起的FAM22B-YWHAE融合基因可能与子宫内膜间质肉瘤发展相关；同时，YWHAE和NUTM2B/E的融合转录本也会导致子宫内膜间质肉瘤的发生。了解YWHAE、NUTM2A和NUTM2B基因重排/融合与恶性肿瘤、YWHAE-FAM22融合基因/易位与肿瘤、YWHAE基因多态性与精神疾病，以及17p13.3区域改变与疾病发生的关系，可为理解YWHAE基因在分子机制与遗传变异方面对疾病进展的作用以及为疾病的靶向治疗提供新的思路和依据。.
Keywords: YWHAE; genetic variation; malignant tumor; mental and neurological diseases.