Dong R, Liu G-B, Liu B-H, Chen G, Li K, Zheng S, Dong K-R
Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China.
Shanghai Key Laboratory of Birth Defect, Shanghai, China.
Cell Death Dis. 2016 Jun 30;7(6):e2278. doi: 10.1038/cddis.2016.143.
Hepatoblastoma is the most common liver tumor of early childhood, which is usually characterized by unusual hypervascularity. Recently, long non-coding RNAs (lncRNA) have emerged as gene regulators and prognostic markers in several cancers, including hepatoblastoma. We previously reveal that lnRNA-TUG1 is upregulated in hepatoblastoma specimens by microarray analysis. In this study, we aim to elucidate the biological and clinical significance of TUG1 upregulation in hepatoblastoma. We show that TUG1 is significantly upregulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. TUG1 knockdown inhibits tumor growth and angiogenesis in vivo, and decreases hepatoblastoma cell viability, proliferation, migration, and invasion in vitro. TUG1, miR-34a-5p, and VEGFA constitutes to a regulatory network, and participates in regulating hepatoblastoma cell function, tumor progression, and tumor angiogenesis. Overall, our findings indicate that TUG1 upregulation contributes to unusual hypervascularity of hepatoblastoma. TUG1 is a promising therapeutic target for aggressive, recurrent, or metastatic hepatoblastoma.
肝母细胞瘤是儿童早期最常见的肝脏肿瘤，其通常以异常的高血管化为特征。最近，长链非编码RNA（lncRNA）已成为包括肝母细胞瘤在内的多种癌症中的基因调节因子和预后标志物。我们之前通过微阵列分析揭示lnRNA-TUG1在肝母细胞瘤标本中上调。在本研究中，我们旨在阐明TUG1上调在肝母细胞瘤中的生物学和临床意义。我们发现TUG1在人肝母细胞瘤标本和转移性肝母细胞瘤细胞系中显著上调。TUG1敲低在体内抑制肿瘤生长和血管生成，并在体外降低肝母细胞瘤细胞的活力、增殖、迁移和侵袭。TUG1、miR-34a-5p和VEGFA构成一个调节网络，并参与调节肝母细胞瘤细胞功能、肿瘤进展和肿瘤血管生成。总体而言，我们的研究结果表明TUG1上调导致肝母细胞瘤异常的高血管化。TUG1是侵袭性、复发性或转移性肝母细胞瘤的一个有前景的治疗靶点。
