Inhibition of HOXB7 suppresses p27-mediated acute lymphoblastic leukemia by regulating basic fibroblast growth factor and ERK1/2

Abstract

AimsAcute lymphoblastic leukemia (ALL) is characterized by abnormal proliferation of immature lymphocytes in the bone marrow, peripheral blood, and other tissues. HOXB7 is upregulated in tumors and is related to cell proliferation and cell cycle. However, the role of HOXB7 in ALL progression remains unclear. In this study, we explored the molecular mechanism of HOXB7 in cell viability and cell cycle in ALL cell lines. Materials and methodsPeripheral blood lymphocytes was isolated by Isopycnic Ficoll-Hypaque solution; Relative mRNA expression of HOXB7 was measured by RT-qPCR; Relative protein expressions of HOXB7, p27, bFGF, pERK1/2 were tested by Western blot assay; Cell viability was tested by MTT; Cell proliferation was detected by BrdU assay; 2.8. Cell cycle was analyzed by flow cytometry. Key findingsHOXB7 was significantly elevated in peripheral blood lymphocytes of patients with ALL. HOXB7 was inhibited by HOXB7 siRNA transfection; cell viability decreased; and cell cycle was arrested in ALL cell lines. Meanwhile, HOXB7 suppression significantly induced the protein expression of p27 (cyclin-dependent kinase inhibitor). We also demonstrated the molecular mechanism of HOXB7 regulation on p27. HOXB7 suppression obviously inhibited the protein expressions of b basic fibroblast growth factor (bFGF) and p-ERK1/2. Also, the inhibitory effects of HOXB7 suppression on p-ERK1/2, cell viability, and cell cycle in ALL cell lines were markedly reversed after culturing with bFGF (9 ng/mL) for 24 h. After incubating with bFGF, cells with HOXB7 inhibition were treated with a specific ERK1/2 inhibitor, PD98095, after which the effects of bFGF on protein expression of p27, cell viability, and cell cycle were obviously reversed. SignificanceOur study suggests that inhibiting HOXB7 suppresses p27-mediated ALL progression by regulating bFGF/ERK1/2.