LncRNA CASC15 promotes tumour progression through SOX4/Wnt/β-catenin signalling pathway in hepatocellular carcinoma (Retracted Article)

LncRNA CASC15 promotes tumour progression through SOX4/Wnt/β-catenin signalling pathway in hepatocellular carcinoma (Retracted Article)
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DOI:
10.1080/21691401.2019.1576713
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发表时间:
2020-01-01
影响因子:
5.8
通讯作者:
Ren, Xuequn
Ren, Xuequn
中科院分区:
工程技术2区
文献类型:
--
作者:
Wang, Chaoyang;Zi, Hao;Ren, Xuequn

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目的:探讨癌易感候选基因cncRNA CASC15在肝细胞癌中的作用及其在Sox4表达和Wnt/β-catenin途径中的调节作用。方法:采用实时定量聚合酶链式反应(QRT-PCR)方法检测肝细胞癌组织中CASC15的相对表达。蛋白质检测采用蛋白质印迹法。用荧光素酶比色法确定CASC15在肝癌中的潜在靶点。分别用四甲基偶氮唑盐比色法、Transwell法和流式细胞仪分析细胞的增殖、迁移和侵袭以及细胞的凋亡。结果:CASC15在肝细胞癌组织中的表达显著升高(P<0.01),且与肿瘤大小(P=0.016)、TNM分期(P=0.018)和转移(P=0.021)呈正相关。CASC15基因的敲除在体外能明显抑制肝癌细胞的增殖、迁移和侵袭,促进细胞凋亡(P&lt;0.05)。此外,抑制CASC15后,Sox4、β-catenin、Cyclin D1和c-Myc的蛋白水平也呈下降趋势。荧光素酶分析证实Sox4可能是CASC15在肝细胞癌中的靶向基因。结论:在肝细胞癌中,CASC15可能通过上调Sox4的表达而激活Wnt/β-catenin通路,从而促进肿瘤的进展。
Objective: The present study aimed to investigate the function of lncRNA CASC15 (cancer susceptibility candidate 15) in hepatocellular carcinoma (HCC), as well as its regulatory roles in SOX4 expression and Wnt/beta-catenin pathway. Methods: Quantitative real-time polymerase chain reaction (QRT-PCR) method was used to detect the relative expression of CASC15 mRNA in HCC tissues. Protein detection was performed by western blot. Luciferase assay was used to confirm the potential target of CASC15 in HCC. Cell proliferation, migration and invasion, as well as apoptosis were analyzed using MTT, transwell assays and flow cytometry in vitro, respectively. Results: The expression of CASC15 was significantly increased in HCC tissues (p < .001) and showed positive correlation with tumour size (p = .016), TNM stage (p = .018) and metastasis (p = .021). The knockdown of CASC15 could obviously inhibit HCC cell proliferation, migration and invasion and promote cell apoptosis in vitro (p < .05 for all). Furthermore, the protein levels of SOX4, beta-catenin, Cyclin D1 and c-Myc also exhibited decreased trends after CASC15 inhibition. Luciferase assay confirmed that SOX4 might be a targeted gene of CASC15 in HCC. Conclusion: In HCC, CASC15 may activate the Wnt/beta-catenin pathway via enhancing the expression of SOX4, thus promote tumour progression.