B Song1, Y-J Tang, W-G Zhang, C-C Wan, Y Chen, L-J Zhang. 1. Department of Hematology, Affiliated Taihe Hospital of Xi'an Jiaotong University Health Science Center, Shiyan, Hubei, China. kansong96417@163.com.
Abstract
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.
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. APLpatients 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.
Authors: Bei Xie; Linjing Li; Zhewen Zhang; Lei Zhao; Juan Cheng; Cunmin Zhou; Jie Cheng; Jing Yan; Jing Chen; Juan Yi; Bei Wang; Suya Jin; Hulai Wei Journal: J Cancer Date: 2021-05-13 Impact factor: 4.207