Abstract：
Hepatoblastoma is the most common type of hepatic tumors occurring in children between 0 and 5 years. And the exact pathophysiology of the disease is still mysterious. Accumulating studies on LncRNA have shown its pivotal role in the development and progression of distinct human cancers. However, the role of LINC01023 in hepatoblastoma is unknown. The relative expression of LINC01023, miR-378a-5p, and Wnt3 on hepatoblastoma tissue and cell lines was determined by quantitative polymerase chain reaction (qRT-PCR). The effect of LINC01023 downregulation and upregulation on cell proliferation, colony formation and apoptosis activities in HUH6 and HepG2 Cells was assessed by CKK8, clonogenic and flow cytometry analysis, respectively. Dual luciferase, RNA immunoprecipitation (RIP), and RNA pull-down were performed to confirm the interaction between LINC01023 and miR-378a-5p. Similarly, Dual luciferase assay was performed to confirmed the interaction between Wnt3 and miR-378a-5p. The xenograft tumorgenicity test was performed to elucidate the tumorgenicity potential of LINC01023. LINC01023 was significantly upregulated in hepatoblastoma tissue and cell lines rather than in adjacent normal hepatic tissue and QSG7701 cell lines. LINC01023 silencing attenuated cell proliferation, colony formation and increased cell apoptosis. Conversely, LINC01023 upregulation results in significant increase in cell proliferation, and colony formation activities however, a significant reduction in apoptosis activity was reported. Interaction between the LINC01023 and WNT3 was confirmed by dual luciferase assay. Xenograft animal tumorgenicity test confirmed the in-vivo tumorigenesis potential of LINC01203. To the best of our knowledge, this study is the first study demonstrating the role of LINC01023 in hepatoblastoma tumorigenesis through the LINC01023/miR-378a-5p/Wnt3 axis. It could be a potential therapeutic target and a prognostic biomarker in hepatoblastoma.
摘要：
肝母细胞瘤是发生在0至5岁儿童中的最常见类型的肝肿瘤。这种疾病的确切病理生理学仍然是神秘的。对LncRNA的大量研究表明其在不同人类癌症的发展和进展中的关键作用。然而,LINC01023在肝母细胞瘤中的作用尚不清楚.LINC01023,miR-378a-5p,通过定量聚合酶链反应（qRT-PCR）测定肝母细胞瘤组织和细胞系上的Wnt3。LINC01023下调和上调对细胞增殖的影响，通过CKK8，克隆和流式细胞术分析评估HUH6和HepG2细胞中的集落形成和凋亡活性，分别。双荧光素酶,RNA免疫沉淀(RIP),和RNA下拉以确认LINC01023和miR-378a-5p之间的相互作用。同样，进行双荧光素酶测定以证实Wnt3和miR-378a-5p之间的相互作用。进行异种移植物致瘤性测试以阐明LINC01023的致瘤性潜力。LINC01023在肝母细胞瘤组织和细胞系中而不是在邻近的正常肝组织和QSG7701细胞系中显著上调。LINC01023沉默减弱细胞增殖，集落形成和细胞凋亡增加。相反，LINC01023上调导致细胞增殖显著增加，和菌落形成活动，据报道，细胞凋亡活性显着降低。LINC01023和WNT3之间的相互作用通过双荧光素酶测定来确认。异种移植动物致瘤性测试证实了LINC01203的体内肿瘤发生潜力。据我们所知,这项研究是第一项通过LINC01023/miR-378a-5p/Wnt3轴证明LINC01023在肝母细胞瘤肿瘤发生中的作用的研究.它可能是肝母细胞瘤的潜在治疗靶标和预后生物标志物。
