Enforced miR-144-3p Expression as a Non-Invasive Biomarker for the Acute Myeloid Leukemia Patients Mainly by Targeting NRF2.

Related Articles

Enforced miR-144-3p Expression as a Non-Invasive Biomarker for the Acute Myeloid Leukemia Patients Mainly by Targeting NRF2.

Clin Lab. 2017 Apr 01;63(4):679-687

Authors: Sun X, Liu D, Xue Y, Hu X

Abstract
BACKGROUND: MicroRNAs (miRNAs) are endogenous non-coding RNAs of 19-25 nucleotides in length. Abnormal miRNA expression has been identified in various types of cancer. However, the aberrant expression of miR-1244 has not been reported in acute myeloid leukemia.
METHODS: First, the expression of miR-144-3p was explored in the bone marrow and peripheral blood of AML patients and healthy control. Then, we also evaluated the level of miR-144-3p in HL-60 cells. The possible target gene of miR-144-3p was predicted using TargetScan. Dual luciferase reporter assay was applied to validate the target gene of miR-144-3p. Cell viability and apoptosis on miR-144-3p was explored. Western blot analysis was applied to identify the downstream signaling of miR-144-3p.
RESULTS: Our data showed that miR-144-3p was markedly increased in both the peripheral blood and bone marrow of AML patients compared with healthy controls. Moreover, we also found an increased expression of miR144-3p in HL-60 cells. In comparison, NRF2 protein expression was significantly decreased in HL-60 cells. Dual luciferase reporter assays demonstrated that miR-144-3p significantly suppressed the relative luciferase reporter activity of a pmirGLO-NRF2-3'UTR. In accordance with the downstream effects of NRF2 overexpression, inhibition of miR-144-3p reduced cell viability and prompted apoptosis. More importantly, we found that the inhibition of miR-144-3p in HL-60 cells could not enhance Caspase-3 activation when NRF2 protein expression was silenced.
CONCLUSIONS: These findings suggest a potential oncogenic function of miR-144-3p in HL-60 cells, which is mainly achieved by targeting NRF2.

PMID: 28397476 [PubMed - in process]

http://ift.tt/2oAao5G