Long noncoding RNA PVT1 promotes hepatoblastoma cell proliferation through activating STAT3.

Abstract

BackgroundHepatoblastoma is the most common liver malignancy in children. The long noncoding RNA (IncRNA) PVT1 plays oncogenic roles in human cancers; however, its regulation and function in hepatoblastoma remain poorly understood.PurposeThis study was designed to investigate the regulation and function of PVT1 in hepatoblastoma. MethodsPVT1 expression was compared between human hepatoblastoma tissues and adjacent non-tumor tissues, and then analyzed using Kaplan-Meier method. The proliferation of hepatoblastoma cells was determined by BrdU incorporation assay. The tumor xenograft model was used to assess tumor proliferation in vivo. The gene expression level was measured by qRT-pCR, Western blot and immunohistochemistry analyses.ResultsCompared with normal counterparts, PVT1 is upregulated in human hepatoblastoma tissues as well as in hepatoblastoma cell lines. Additionally, PVT1 promotes the proliferation of hepatoblastoma cells in vitro and accelerates tumor growth in xenograft model in vivo. Mechanistically, PVT1 promotes the activation of the signal transducer and activator of transcription 3 (STAT3), which leads to the transcriptional activation of downstream targets involved in cell cycle progression, and moreover,STAT3 inhibition with the selective inhibitor stattic abolishes PVT1 pro-proliferative role in hepatoblastoma cells.ConclusionPVT1 promotes hepatoblastoma cell proliferation through activating STAT3-induced cell cycle progression, which may implicate PVT1 as a potential therapeutic target for hepatoblastoma treatment.