OBJECTIVE: Extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling pathway is widely involved in cell proliferation and invasion regulation. Enhanced expression or function of ERK1 is important for leukemia. Abnormal down-regulation of microRNA (miR)-143 is correlated with leukemia pathogenesis, indicating possible tumor-suppressing role. Bioinformatics analysis showed the existence of complementary binding sites between miR-143 and ERK1. This study aims to investigate whether the miR-143 plays a role in mediating ERK1 expression and proliferation and apoptosis of leukemia cells.
PATIENTS AND METHODS: Dual luciferase reporter gene assay confirmed targeted regulation between miR-143 and ERK1. Quantitative RT-PCR (qRT-PCR) was used to measure and compare the peripheral miR-143 and ERK1 expression between healthy and acute promyelocytic leukemia (APL) patients to analyze the effect of miR-143 and MEK1 on survival and prognosis. Cultured HL-60 cells were treated with miR-143 mimic or small interfering RNA (siRNA)-ERK1, followed by qRT-PCR to measure miR-143 expression. Western blot quantified expression of ERK1 and p-ERK1, flow cytometry measured apoptosis, and EdU staining measured proliferation.
RESULTS: MiR-143 targeted and modulated ERK1. APL patients presented lower miR-143 and higher ERK1 in peripheral blood. Those with miR-143 down-regulation displayed worse prognosis than those with high miR-143 expression (χ2 = 5.198, p = 0.039). Patients with ERK1 mRNA low-expression presented better prognosis than those a having higher expression (Log-rank test, χ2 = 5.873, p = 0.028). Transfection of miR-143 mimic or siRNA-ERK1 remarkably suppressed ERK1 and p-ERK1 expression in HL-60 cells, inhibited cell proliferation and induced cell apoptosis.
CONCLUSIONS: MiR-143 down-regulation and ERK1 up-regulation are correlated with APL pathogenesis. Their expression level affected patient’s prognosis. MiR-143 targeted and inhibited ERK1 expression, weakened proliferation potency of HL-60 cells, and induced apoptosis.Free PDF Download
To cite this article
B. Song, Y.-J. Tang, W.-G. Zhang, C.-C. Wan, Y. Chen, L.-J. Zhang
MiR-143 regulates proliferation and apoptosis of myelocytic leukemia cell HL-60 via modulating ERK1
Eur Rev Med Pharmacol Sci
Vol. 22 - N. 11