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

Yuan,Miao-Xian; Ji,Chun-Yi; Gao,Hong-Qiang; Sheng,Xin-Yi; Xie,Wei-Xin; Yin,Qiang

doi:10.3892/mmr.2021.12192

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

Authors:
- Miao-Xian Yuan
- Chun-Yi Ji
- Hong-Qiang Gao
- Xin-Yi Sheng
- Wei-Xin Xie
- Qiang Yin
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Affiliations: Department of General Surgery, Hunan Children's Hospital General Surgery, Changsha, Hunan 410007, P.R. China
Published online on: June 2, 2021 https://doi.org/10.3892/mmr.2021.12192
Article Number: 553

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Abstract

Hepatoblastoma is the most common malignant hepatic tumour type with hypervascularity in early childhood. 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 activating the downstream signalling pathway of JAK2/STAT3 to facilitate angiogenesis. The present findings will provide novel targets for the treatment of hepatoblastoma.

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