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Identification of the downstream signaling pathways of HOXA5 in breast cancer cells
ZHANG Li-mei ZHAN Jun ZHANG Hong-quan XUE Li-xiang*
Acta Anatomica Sinica ›› 2015, Vol. 46 ›› Issue (5) : 634-640.
Identification of the downstream signaling pathways of HOXA5 in breast cancer cells
Objective To investigate the role of transcriptional factor HOXA5 in breast cancer progression. Methods Stably transfected BT549 and SUM159 cell lines with overexpression of HOXA5 were established. Transwell assay, Western blotting and colony formation were applied to detect cell migration, the expression of epithelial-mesenchymal transition (EMT) markers and cell proliferation respectively. RNA-seq was further performed to investigate the target genes of HOXA5. Software Cluster 3.0, treeview, database DAVID Bioinformatics Resources and Enrichr were used to analyze the pathways in Kyoto Encyclopedia of Genes and Genomes (KEGG) and draw the heatmap. Results In BT549 cells, stable transfection of HOXA5 repressed cell migration(P<0.05), promoted expression of E-cadherin and repressed expression of N-cadherin, Twist1 and Slug. HOXA5 repressed colony formation(P<0.05) and cell proliferation as well. Conclusion Our results reveal that HOXA5 represses cell migration by promoting the transition from mesenchymal to epithelial. RNA-seq results show that HOXA5 may inhibit cancer cell proliferation by regulating glucose and lipid metabolism and may repress cell migration by targeting genes related with cell motility and cell adhension. In addition, HOXA5 may play an anticancer role by regulating tumor necrosis factor (TNF) pathway. Based on these data, we conclude that transcriptional factor HOXA5 represses breast cancer progression and may act as a breast cancer repressor.
HOXA5 / Breast cancer / Epithelial-mesenchymal transition / Transwell / RNA-Sequence
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