Effect of miR-21 on apoptosis in hepatoblastoma cell through activating ASPP2/p38 signaling pathway in vitro and in vivo

Abstract

The objective of this study was to investigate the mechanism underlying miR-21-associated apoptosis in HB. In this study, HB and adjacent tissues were collected from patients with HB. RT-PCR, FISH, western blot, apoptosis assay, migration, invasion and wound healing assays, caspase activity assay, luciferase reporter assays, and xenografts mouse model were used to determine the effects of miR-21 on HB cell apoptosis. The results revealed that miR-21 was up-regulated in both HB cell and tissue and was associated with progression of HB. MiR-21 inhibitor enhanced the apoptosis level in HB cells. MiR-21 inhibitor showed reduced abilities of migration and invasion. ASPP2 was a target gene of miR-21. Inhibition of ASPP2 increased abilities of migration and invasion in HB cells. Furthermore, miR-21 inhibitor caused increased activity p-38 signaling. In a xenografts mouse model, miR-21 inhibitor could significantly suppress tumor growth in nude mice along with enhanced expressions of ASPP2 and p38. Taken together, the results suggest that upregulation of miR-21 is related to HB progression and miR-21-associated apoptosis in HB is mediated through ASPP2/p38 signaling pathway in vitro and in vivo. This study provides novel insight into the effects of miR-21 on HB apoptosis and clue to develop new therapies.

Keywords

• MiR-21
• hepatoblastoma
• apoptosis
• ASPP2
• p38