lncRNA TUG1 regulates angiogenesis via the miR-204-5p/JAK2/STAT3 axis in hepatoblastoma

Abstract

Hepatoblastoma is the most common malignant hepatic tumour type with hypervascularity in early child- hood. in recent decades, emerging evidence has proven that long non-coding rnas (lncrnas) serve an important oncogenic role in the pathogenesis of hepatoblastoma. However, the underlying mechanism of lncrna taurine upregulated 1 (TuG1) in the angiogenesis of hepatoblastoma remains unknown. The expression patterns of TuG1 and microrna (mir)-204-5p were detected in hepatoblastoma tissues and cell lines via reverse transcription-quantitative Pcr and were analysed using a Pearson's correlation test. a tube formation assay was performed using human umbilical vein endothelial cells to assess the vasculogenic activity of treated HuH-6 cells. eliSa was used to detect the level of the secretory proangiogenic factor VeGFa in the culture media of HuH-6 cells. a dual luciferase reporter assay was performed to validate the binding relationships of TuG1/mir-204-5p and mir-204-5p/Janus kinase 2 (JaK2). Moreover, western blotting was conducted to measure the protein expression levels of VeGFa, phosphorylated (p)-JaK2, JaK2, p-STaT3 and STaT3. it was identified that TuG1 was upregulated, while mir-204-5p was downregulated in hepatoblastoma tissues and cells. TuG1 knockdown inhibited angiogenesis induced by hepatoblastoma cells. Furthermore, mir-204-5p was identified as a target of TUG1. The results demonstrated that TuG1 attenuated the inhibitory effect of mir-204-5p on the JaK2/STaT3 pathway and promoted angiogenesis in hepatoblastoma cells. in summary, TuG1 was upregulated in hepatoblastoma and suppressed mir-204-5p, thereby acti- vating the downstream signalling pathway of JaK2/STaT3 to facilitate angiogenesis. The present findings will provide novel targets for the treatment of hepatoblastoma.