Background and Aims: Although a certain progress has been made in the treatment of hepatoblastoma (HB) in children, the overall clinical prognosis is still poor. So, exploring its pathogenesis and effective therapeutic targets are of great importance. This study was conducted to investigate the expressions of the long non-coding RNA taurine-upregulated gene 1 (TUG1) and the molecules associated with JAK2-STAT3 pathway in HB tissue and preliminarily analyze the relationship between TUG1 and miR-204-mediated JAK2-STAT3 angiogenic signaling pathway. 
Methods: Sixty pediatric patients with HB admitted in Hunan Children’s Hospital from March 2017 to April 2018 were enrolled as study subjects. The HB tumor tissues along with the tumor-adjacent normal tissues of the patients were collected. The protein expressions of JAK2, STAT3 and their downstream angiogenesis-related molecules in the tissue samples were detected by immunohistochemical staining and Western blot, respectively. The RNA expressions of TUG1 and miR-204 as well as JAK2 and STAT3 and their downstream angiogenesis-related molecules in the tissue samples were determined by qRT-PCR method, and the correlation between TUG1 and miR-204 expressions in HB tissue was analyzed. Moreover, in human HB cell line HepG2, the changes in RNA and protein expression levels of JAK2, STAT3 and their downstream angiogenesis-related molecules were analyzed after TUG1 knockdown or miR-204 overexpression.
Results: The results of immunohistochemical staining showed that the positive expression rates of both JAK2 and STAT3 HB tissue were significantly higher than those in tumor-adjacent normal tissue (JAK2: 40.1% vs. 16.9%; STAT3: 55.7% vs. 19.8%, both P<0.05). The results of qRT-PCR showed that the RNA expression levels of TUG1, miR-204 as well as JAK2 and STAT3 and their downstream angiogenesis-related molecules that included VEGF, VEGFR2 and HIF-1α were significantly up-regulated in HB tissue than those in tumor-adjacent normal tissue (all P<0.05), and there was a significant negative correlation between TUG1 and miR-204 expressions in HB tissue (r=–0.962, P=0.014). The results of Western blot showed that the protein expression levels of JAK2 and STAT3 and their downstream angiogenesis-related molecules were significantly upregulated in HB tissue than those in tumor-adjacent normal tissue (all P<0.05). In HepG2 cells after TUG1 knockdown or miR-204 overexpression, the RNA and protein expressions of JAK2 and STAT3 and their downstream angiogenesis-related molecules were significantly down-regulated (all P<0.05).
Conclusion: In the tumor tissues from HB children, the expressions of TUG1 is up-regulated, accompanied with the increased activity of JAK2-STAT3 pathway, and there is also a negative correlation between TUG1 and miR-204 expressions. These findings suggest that TUG1 can probably activating the JAK2-STAT3 pathway and thereby promote the angiogenesis through inhibiting miR-204 expression in HB.