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

• Published in: Artificial cells, nanomedicine, and biotechnology Vol. 47; no. 1; pp. 3729 - 3736
• Main Authors: Liu, Lili, Wang, Likun, Li, Xidong, Tian, Ping, Xu, Hao, Li, Zenglian, Liu, Enqin
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 04.12.2019; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Animals; Apoptosis; Apoptosis - genetics; Apoptosis Regulatory Proteins - metabolism; ASPP2; Assaying; Caspase; Cell Line, Tumor; Cell Proliferation - genetics; Cell Transformation, Neoplastic; Gene Expression Regulation, Neoplastic; hepatoblastoma; Hepatoblastoma - genetics; Hepatoblastoma - pathology; Humans; In vivo methods and tests; Inhibitors; Kinases; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Male; Mice; MicroRNAs - genetics; MiR-21; p38; p38 Mitogen-Activated Protein Kinases - metabolism; Polymerase chain reaction; Signal transduction; Signal Transduction - genetics; Signaling; Wound healing; Xenografts; Xenotransplantation; hepatoblastoma; apoptosis; ASPP2; MiR-21; p38
• ISSN: 2169-1401; 2169-141X
• DOI: 10.1080/21691401.2019.1664561

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.