Department of Clinical Laboratory Medicine, Shanghai Tenth Peoples Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, People's Republic of China.
Department of Orthopedics, Tongji Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200065, People's Republic of China.
Mol Cell Biochem. 2023 Aug;478(8):1867-1885. doi: 10.1007/s11010-022-04636-5. Epub 2022 Dec 28.
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.
肝癌是儿童 0 至 5 岁之间最常见的肝肿瘤类型。疾病的确切病理生理学仍然神秘。越来越多的关于长链非编码 RNA（lncRNA）的研究表明，它在不同人类癌症的发生和发展中起着关键作用。然而，LINC01023 在肝癌中的作用尚不清楚。通过实时定量聚合酶链反应（qRT-PCR）测定肝癌组织和细胞系中 LINC01023、miR-378a-5p 和 Wnt3 的相对表达。通过 CKK8、集落形成和流式细胞术分析分别评估 LINC01023 下调和上调对 HUH6 和 HepG2 细胞增殖、集落形成和凋亡活性的影响。双荧光素酶报告基因、RNA 免疫沉淀（RIP）和 RNA 下拉实验证实 LINC01023 与 miR-378a-5p 的相互作用。同样，双荧光素酶实验证实了 Wnt3 与 miR-378a-5p 的相互作用。进行异种移植肿瘤发生试验以阐明 LINC01023 的致瘤潜力。LINC01023 在肝癌组织和细胞系中显著上调，而在相邻正常肝组织和 QSG7701 细胞系中则没有上调。LINC01023 沉默减弱了细胞增殖、集落形成并增加了细胞凋亡。相反，LINC01023 的上调导致细胞增殖和集落形成活性显著增加，而凋亡活性显著降低。双荧光素酶报告基因证实了 LINC01023 与 WNT3 的相互作用。异种移植动物肿瘤发生试验证实了 LINC01203 的体内致瘤潜力。据我们所知，这项研究首次证明了 LINC01023 通过 LINC01023/miR-378a-5p/Wnt3 轴在肝癌肿瘤发生中的作用。它可能成为肝癌的潜在治疗靶点和预后生物标志物。
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