YWHAB is regulated by IRX5 and inhibits the migration and invasion of breast cancer cells

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Abstract
Highly metastatic and heterogeneous breast cancer affects the health of women worldwide. Abnormal expression of tyrosine 3‑monooxygenase/tryptophan 5‑monooxygenase activation protein β (YWHAB), also known as 14‑3‑3β, is associated with the tumorigenesis and progression of bladder cancer, lung cancer and hepatocellular carcinoma; however, to the best of our knowledge, the role of YWHAB in breast cancer remains unknown. In the present study, a dual luciferase assay demonstrated that the transcription factor iroquois homeobox 5 may regulate YWHAB expression by affecting the promoter sequence upstream of its transcription start site. Subsequently, it was demonstrated that overexpression of YWHAB did not affect proliferation, but did reduce the migration and invasion of MDA‑MB‑231 cells. Furthermore, knockdown of YWHAB promoted the migration and invasion of MCF7 cells. Transcriptomics analysis demonstrated that when YWHAB was overexpressed, 61 genes were differentially expressed, of which 43 genes were upregulated and 18 genes were downregulated. These differentially expressed genes (DEGs) were enriched in cancer‑related pathways, such as ‘TNF signaling pathway’ [Kyoto Encyclopedia of Genes and Genomes (KEGG): map04688]. The pathway with the largest number of DEGs was ‘Rheumatoid arthritis’ (KEGG: map05323). Notably, YWHAB downregulated vimentin, which is a mesenchymal marker, thus suggesting that it may weaken the mesenchymal properties of cells. These findings indicate that YWHAB may be a potential therapeutic target in breast cancer and further work should be performed to assess its actions as a potential tumor suppressor.

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