Background: HuR/ELAVL1 (embryonic lethal abnormal vision 1) protein exerts important prognostic effects of involving in the pathogenesis and development of acute myeloid leukemia (AML). This study aims to investigate the role of HuR targeted by miR-29b-3p in biological behaviors of AML cells and the involvement of the NF-κB and JAK/STAT signaling pathways.
Methods: The expressions of HuR and miR-29b-3p were determined using real-time quantitative PCR and Western blot analysis, and the association between them was analyzed using the Spearman’s coefficient correlation. Next, the potential relationship between HuR and miR-29b-3p was predicted based on data from different biological information databases and verified by the Dual-luciferase reporter gene assay. The effect of miR-29b-3p-meidated HuR expressions on the biological behaviors of AML cells was explored after transfecting lentiviruses, mimics, and inhibitors against miR-29b-3p into AML cells. Then, the expression patterns of Bcl-2 and Bax were detected to understand the apoptosis effect of HuR on AML cells. Phosphorylation levels of NF-κB /p65, IκBα, STAT1, STAT3 and STAT5 were determined to assess the influence of HuR on AML as well as the relationship between the NF-κB and JAK/STAT signaling pathways.
Results: HuR was negatively correlated with miR-29b-3p, which was thereby identified as a downstream target of miR-29b-3p in AML. When miR-29b-3p was overexpressed in AML cells, HuR expression was lowered, accompanied by inhibited cell proliferation, migration and invasion, decreased Bcl-2 and Bax levels, as well as inhibited phosphorylation levels of p65, IκBα, STAT1, STAT3 and STAT5.
Conclusion: HuR is a direct target of miR-29b-3p. Lowered HuR protein expression by miR-29b-3p inhibits the malignant biological behaviors of AML cells via the inactivation of the NF-κB and JAK/STAT pathways. Key words: HuR, miR-29b-3p, malignant biological behaviors, the NF-κB and JAK/STAT signaling pathways, acute myeloid leukemia