Fig. 1

Schematic diagram of HOXA9-mediated signaling pathways. HOXA9 as a transcription factor can regulate multiple genes involving in proliferation, apoptosis, differentiation and metastasis such as RUNX2, IGF1, CYBB, BCL-2, SOX2 via binding to their promoters. Abnormal expression of HOXA9 is associated with multiple signaling pathways. HOXA9 promotes apoptosis and represses autophagy through regulating genes RELA, BCL-XL, ULK1, ATG3, and ATG12 associated with NF-κB signaling pathway. HOXA9 regulates glycolysis through blocking HIF-1a binding to glucose metabolism associated genes such as GLUT1, PGK1, and PDK1. HOXA9 was also associated with JAK/STAT pathway through enhancing the transcription activity of STAT5, leading to the upregulation of its downstream target genes FOS, JUN. Deregulation of HOXA9 is often accompanied by alteration of Wnt/β-catenin signaling. HOXA9 as a direct target of miR-429 regulates Wnt/β-catenin signaling pathway through regulation of β-catenin, c-myc, c-jun expression. Abnormal expression of HOXA9 also leads to the alteration of PI3K/Akt signaling pathway. Overexpression of HOXA9 promotes the ability of proliferation, invasion, and migration through upregulating the expression of p-PI3K, p-Akt, Cyclin D, C-Myc, MMP2, and MMP9