Characterization of hsa_circ_0000594 as a new biomarker and therapeutic target for hepatoblastoma

Characterization of hsa_circ_0000594 as a new biomarker and therapeutic target for hepatoblastoma
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hsa_circ_0000594 作为肝母细胞瘤新生物标志物和治疗靶点的表征

DOI:
10.26355/eurrev_201910_19138
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发表时间:
2019-01-01
影响因子:
3.3
通讯作者:
Zheng, L.
Zheng, L.
中科院分区:
医学4区
文献类型:
--
作者:
Song, H.;Bian, Z-X;Zheng, L.

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目的:大量研究表明,环状RNA(circRNA)的异常表达在多种肿瘤中起着关键作用。然而,circRNA在肝母细胞瘤(HB)中的作用尚不清楚。在本研究中,我们试图探讨hsa_circ_0000594在HB的潜在机制,沿着其临床importance.PATIENTS和METHODS:在我们的研究中,hsa_circ_0000594在HB组织和匹配的正常肝组织中的表达模式,通过原位杂交和RT-qPCR确定。采用CCK-8、集落形成、transwell和流式细胞术检测HB细胞系的增殖、活力、迁移和凋亡。结果:hsa_circ_0000594在HB组织中的表达水平显著高于正常肝组织,且与HB亚型相关。hsa_circ_0000594的敲低抑制了HB的恶性表型。结论:hsa_circ_0000594通过hsa_circ_0000594/mir-217/SIRT 1调控轴在HB发生发展中发挥重要作用,可能成为HB诊断的新标志物和潜在的治疗靶点。
OBJECTIVE: Various studies have shown that aberrant expression of circular RNAs (circRNAs) has a pivotal role in multifarious cancers. However, the role of circRNAs in hepatoblastoma (HB) is not clearly understood. In the present study, we attempted to explore the underlying mechanism of hsa_cric_0000594 in HB along with its clinical importance.PATIENTS AND METHODS: In our research, the expression pattern of hsa_circ_0000594 in HB tissues and matched normal liver tissues was determined by in situ hybridization and RT-qPCR. Proliferation, viability, migration, and apoptosis of HB cell lines were detected via Cell Counting Kit-8 (CCK-8), colony formation, transwell, and flow cytometry assays. The interaction of hsa_circ_0000594 with miR-217 was investigated by Dual-Luciferase reporter assay.RESULTS: Expression levels of hsa_circ_0000594 were significantly upregulated in HB tissues compared with those in paired normal liver tissues and showed a clear association with the subtype of HB. The knockdown of hsa_circ_0000594 inhibited the malignant phenotype of HB. Bioinformatics analysis suggests that sirtuin 1 (SIRT1) may serve as a target gene of miR-217.CONCLUSIONS: Mechanically, hsa_circ_0000594 was identified to have a critical role in HB development through the hsa_circ_0000594/mir-217/SIRT1 regulatory axis, which might become a novel diagnostic marker and potential therapeutic target in HB.