Targeting long non-coding RNA-TUG1 inhibits tumor growth and angiogenesis in hepatoblastoma.

Targeting long non-coding RNA-TUG1 inhibits tumor growth and angiogenesis in hepatoblastoma.
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DOI:
10.1038/cddis.2016.143
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发表时间:
2016-06-30
影响因子:
9
通讯作者:
--
中科院分区:
生物学1区
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肝母细胞瘤是儿童早期最常见的肝脏肿瘤,通常以异常的富血供为特征。最近,长链非编码RNA(lncRNA)已成为包括肝母细胞瘤在内的几种癌症的基因调控因子和预后标志物。我们先前通过微阵列分析揭示了肝母细胞瘤标本中lnRNA-TUG 1的上调。在这项研究中,我们的目的是阐明肝母细胞瘤中TUG 1上调的生物学和临床意义。我们发现TUG 1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。TUG 1敲低抑制体内肿瘤生长和血管生成,并降低体外肝母细胞瘤细胞活力、增殖、迁移和侵袭。TUG 1、miR-34 a-5 p和VEGFA构成调控网络,参与调控肝母细胞瘤细胞功能、肿瘤进展和肿瘤血管生成。总的来说,我们的研究结果表明,TUG 1上调有助于肝母细胞瘤不寻常的血管丰富。TUG 1是侵袭性、复发性或转移性肝母细胞瘤的有希望的治疗靶点。
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.
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