OObjective: Long non-coding RNA (lncRNA) H19 has essential roles in growth, migration, invasion, and metastasis of most cancers. H19 dysregulation is present in a large number of solid tumors and leukemia. However, the expression level of H19 in acute lymphoblastic leukemia (ALL) has not been elucidated yet. The current study aimed to explore H19 expression in ALL patients and cell lines.
Materials and methods: This experimental study was conducted in bone marrow (BM) samples collected from 25 patients with newly diagnosed ALL. In addition, we cultured the RPMI-8402, Jurkat, Ramos, and Daudi cell lines and assessed the effects of internal (hypoxia) and external (chemotherapy medications L-asparaginase [ASP] and vincristine [VCR]) factors on h19 expression. The expressions of H19, P53, c-Myc, HIF-1α and β-actin were performed using quantitative real-time polymerase chain reaction (qRT-PCR) method.
Results: There was significantly increased H19 expression in the B-cell ALL (B-ALL, P<0.05), T-cell ALL (T-ALL, P<0.01) patients and the cell lines. This upregulation was governed by the P53, HIF-1α, and c-Myc transcription factors. We observed that increased c-Myc expression induced H19 expression; however, P53 adversely affected H19 expression. In addition, the results indicated that chemotherapy changed the gene expression pattern. There was a considerable decrease in H19 expression after exposure to chemotherapy medications; nonetheless, hypoxia induced H19 expression through P53 downregulation.
Conclusion: Our findings suggest that H19 may have an important role in pathogenesis in ALL and may act as a promising and potential therapeutic target.
Keywords: Acute lymphoblastic leukemia; H19; Hypoxia; lncRNA.