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  • Title: LncRNA ANRIL promotes cell proliferation, migration and invasion during acute myeloid leukemia pathogenesis via negatively regulating miR-34a.
    Author: Wang CH, Li QY, Nie L, Ma J, Yao CJ, Chen FP.
    Journal: Int J Biochem Cell Biol; 2020 Feb; 119():105666. PubMed ID: 31830533.
    Abstract:
    OBJECTIVE: LncRNA ANRIL (antisense non-coding RNA in the INK4 locus) was highly expressed in acute myeloid leukemia (AML) patients to promote AML pathogenesis. In this study, we aimed to investigate the roles and molecular events of ANRIL associated with AML progression. METHODS: Expression patterns of ANRIL and miR-34a in the bone marrow (BM) samples and cell lines were determined using qRT-PCR. Cell proliferation, apoptosis, migration and invasion of cells with ANRIL knockdown or miR-34a overexpression were assessed by CCK-8, EdU staining, flow cytometry and Transwell assays, respectively. The dual-luciferase reporter assay was employed to validate the relationship between miR-34a and Histone deacetylase 1 (HDAC1). The binding of E2 F1 (E2 F transcription factor 1) with gene promoter was analyzed by ChIP. Furthermore, the tumorigenicity of AML was determined by xenograft transplantation in nude mice. RESULTS: ANRIL was up-regulated both in the BM samples from AML patients and cell lines (HL-60 and THP-1), of which expression was negatively correlated with miR-34a expression. ANRIL knockdown inhibited cell proliferation, migration and invasion but promoted apoptosis of AML cells, while overexpression of miR-34a exerted opposite effects. miR-34a was verified as a downstream gene targeted by ANRIL. Moreover, HDAC1 was a direct target of miR-34a, and HDAC1 overexpression impaired the recruitment of E2 F1 to ASPP2 (apoptosis stimulating proteins of p53) gene promoter. ANRIL knockdown significantly inhibited the tumorigenesis of AML. CONCLUSION: ANRIL promotes AML development through HDAC1-mediated epigenetic suppression of ASPP2 via negatively regulating miR-34a, which might serve as a therapeutic target for AML treatment.
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