MiR-130a is aberrantly overexpressed in adult acute myeloid leukemia with t(8;21) and its suppression induces AML cell death


Background: Emerging evidence has revealed that miRNAs can function as oncogenes or tumor suppressor genes in leukemia. The ectopic expression of miR-130a has been reported in chronic leukemia, but our understanding of the biological implications of miR-130a expression remains incomplete. Methods: We quantified a cohort of de novo acute myeloid leukemia (AML) by bead-based miRNA and real-time quantitative PCR (Rq-PCR). The luciferase reporter gene assay was analyzed after the plasmid constructs which contain 5’-UTR of miR-130a and a Renilla luciferase reporter plasmid were transfected simultaneously into 293T cells. MTT and caspase 3/7 apoptosis assays were used to test cell viability and apoptosis. Results: We identified miR-130a as significantly overexpressed in t(8;21) AML. Expression of miR-130a decreased significantly once patients with t(8;21) achieved complete remission, but increased sharply at the time of relapse. In patients with t(8;21) AML, KIT mutational status was associated with miR-130a expression—with higher expression associated with KIT activating mutations. Increased miR-130a expression in t(8;21) AML was associated with slightly worse event-free survival; however, no impact on overall survival was observed. Knockdown of AML1/ETO protein in the SKNO-1 cell line resulted in decrease of expression of miR-130a. Direct binding of AML1/ETO fusion protein with the promoter sequence of miR-130a was detected with luciferase reporter gene assay. Following miR-130a knockdown, SKNO-1 demonstrated increased sensitivity to etoposide. Conclusions: Our data suggest that miR-130a is directly activated by AML1/ETO, and may act as a factor which is associated with leukemia burden, event-free survival, and chemotherapy sensitivity in t(8;21) AML

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oai:doaj.org/article:d9a61acf99c746f9aab67c61241a5722Last time updated on 6/4/2019

This paper was published in Directory of Open Access Journals.

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