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

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).