LncRNA OIP5-AS1 aggravates the stemness of hepatoblastoma through recruiting PTBP1 to increase the stability of β-catenin.

Background: Hepatoblastoma is a malignancy that occurs in the liver, most of which occur in children younger than 3 years old. It was reported that lncRNA OIP5-AS1 was up-regulated in hepatoblastoma, but the detailed mechanism by which OIP5-AS1 regulates hepatoblastoma development is unclear.

Methods: qRT-PCR, Western blotting, and immunofluorescence were used to examine levels of OIP5-AS1, PTBP1, β-catenin or proliferation/stemness-related molecules. Colony formation, sphere formation, wound healing assay and transwell were applied to detect cell proliferation, stemness and invasion, respectively. RIP assay was used to investigate the interaction of OIP5-AS1/PTBP1 and PTBP1/CTNNB1. Finally, in vivo model was constructed to detect the function of OIP5-AS1 in hepatoblastoma.

Results: OIP5-AS1 was significantly up-regulated in hepatoblastoma cells. OIP5-AS1 silencing notably attenuated the stemness and invasion of hepatoblastoma cells. OIP5-AS1 bound with PTBP1, and silencing of OIP5-AS1 inhibited β-catenin. Meanwhile, overexpression of PTBP1 or β-catenin activation significantly reversed OIP5-AS1 silencing-inhibited hepatoblastoma cell proliferation and stemness. Moreover, β-catenin was found to be the downstream target of PTBP1, and OIP5-AS1 activated β-catenin signaling via promoting the binding between PTBP1 and β-catenin to increase the mRNA stability of β-catenin. Finally, OIP5-AS1 knockdown significantly alleviated the tumor growth of hepatoblastoma by repressing β-catenin.

Conclusion: OIP5-AS1 silencing inhibits the growth and stemness of hepatoblastoma through binding with PTBP1 to inhibit β-catenin signaling pathway. OIP5-AS1 may be the potential target against hepatoblastoma.