Linoleic acid derivatives target miR-361-3p/BTG2 to confer anticancer effects in acute myeloid leukemia

Abstract Acute myeloid leukemia (AML) is a deadly hematologic malignancy. Studies have shown that miroRNAs (miRNAs), evolutionarily conserved small noncoding RNAs, contribute to AML disease development, suggesting that therapeutical manipulation of miRNAs may benefit disease treatment in AML. In this study, we found miR-361-3p was significantly upregulated in the blood of AML patients, whereas the expression of its direct target, B-cell translocation gene (BTG2, a tumor suppressor), was markedly lower compared with the expression in the blood of healthy controls. Inhibition of miR-361-3p significantly increased BTG2, leading to inhibition of cell proliferation and promotion of cell apoptosis in AML cell line, HL-60. In contrast, increasing of miR-361-3p expression exerted opposite effects to miR-361-3p inhibitor on BTG2 expression, cell proliferation and apoptosis. We further showed 9s-Hydroxyoctadecadienoic acid (9s-HODE), a major active derivative of linoleic acid, exerted an anti-AML effect through, at least partly, targeting miR-361-3p/BTG2 axis and its associated pathways. These findings not just demonstrate an oncogenic role of miR-361-3p in AML but also provide novel insights to develop a potential therapeutic for AML treatment by manipulating its expressions.