MicroRNA‐26‐5p functions as a new inhibitor of hepatoblastoma by repressing lin‐28 homolog B and aurora kinase a expression

Abstract

Hepatoblastoma (HB) is the most common liver tumor in children. Despite recent improvements in treatment strategies, the survival of children with hepatoblastoma remains poor. In this study, we identified a novel role of microRNA‐26a‐5p (miR‐26a‐5p), lin‐28 homolog B (LIN28B), Ras‐related nuclear protein (RAN), and aurora kinase A (AURKA) in HB. The expression of LIN28B, RAN, and AURKA was significantly up‐regulated in human HB livers and cell lines. Knockdown of LIN28B and RAN by small interfering RNAs inhibited HB tumor cell proliferation and foci formation. We also elucidated miR‐26a‐5p‐mediated translational inhibition of LIN28B and AURKA in HB. Overexpression of miR‐26a‐5p markedly decreased LIN28B and AURKA 3′‐untranslated region activities and protein expression and repressed HB cell proliferation and colony formation. In contrast, re‐expression of LIN28B and AURKA rescued miR‐26a‐5p‐mediated suppression of HB cell growth and clonality. Importantly, a decreased miR‐26a‐5p expression correlated with the poor outcome of patients with HB. Conclusion: miR‐26a‐5p is a newly identified repressor of HB growth through its inhibition of the oncogenic LIN28B–RAN–AURKA pathway. (Hepatology Communications 2018;2:481‐491)