Increased long noncoding RNA LINC00511 is correlated with poor prognosis and contributes to cell proliferation and metastasis by modulating miR-424 in hepatocellular carcinoma

Increased long noncoding RNA LINC00511 is correlated with poor prognosis and contributes to cell proliferation and metastasis by modulating miR-424 in hepatocellular carcinoma
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DOI:
10.26355/eurrev_201904_17691
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发表时间:
2019-04-01
影响因子:
3.3
通讯作者:
Chen, L-X
Chen, L-X
中科院分区:
医学4区
文献类型:
--
作者:
Wang, R-P;Jiang, J.;Chen, L-X

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目的:据报道,长链非编码RNA(IncRNA)在人肝细胞癌(HCC)中异常表达,并与HCC的进展相关。已证实LncRNA LINC 00511(LINC 00511)在几种肿瘤中充当肿瘤促进剂。然而.作为一种新的IncRNA。LINC 00511的具体作用仍然很不清楚。在这项研究中,我们的目的是评估LINC 00511在HCC行为的影响,并阐明其发生的机制。患者和方法:LINC 00511在HCC组织和细胞系的表达进行了评估,通过qRT-PCR。LINC 00511的表达与肝癌患者的临床病理参数和预后之间的相关性使用几种统计学方法来确定。采用CCK-8法、集落形成法、流式细胞术、细胞凋亡法、EdU法、创伤愈合法和transwell法研究LINC 00511对体外培养的肿瘤细胞恶性表型的影响。结果:LINC 00511在肝癌组织和细胞系中表达显著上调,其高表达与肿瘤的淋巴结转移、血管浸润和临床分期密切相关。此外,统计分析显示,具有较高LINC 00511表达水平的HCC患者的总体生存率较差。重要的是,多变量分析证实LINC 00511表达是HCC患者总生存期的独立预后因素。功能上的。抑制LINC 00511显著抑制HCC细胞系的增殖、迁移和侵袭能力。生物信息学方法预测miR-424同时靶向LINC 00511的3 '-UTR,荧光素酶报告基因检测和RT-PCR证实了这一点。结论:LINC 00511通过调控miR-424在HCC的恶性进展中发挥重要作用。
OBJECTIVE: Long noncoding RNAs (IncRNAs) have been reported to be abnormally expressed in human hepatocellular carcinoma (HCC) and associated with the progression of HCC. LncRNA LINC00511 (LINC00511) has been confirmed to act as a tumor promoter in several tumors. However. as a novel IncRNA. the specific effect of LINC00511 is still largely obscure. In this study, we aimed to evaluate the effect of LINC00511 in HCC behaviors and to elucidate the mechanism by which this occurs.PATIENTS AND METHODS: The expressions of LINC00511 in HCC tissues and cell lines were evaluated by qRT-PCR. The correlations between LINC00511 expression and the clinicopathological parameters and prognosis of HCC patients were determined using several statistical methods. CCK-8 assay, colony formation assay, flow cytometry cell cycle, apoptosis assay, EdU assay, wound healing assay, and transwell assay were used to investigate the role of LINC00511 on the malignant phenotypes in vitro. Insights into the potential mechanisms of ceR-NAs were determined by bioinformatics analysis, dual-luciferase reporter assays and RT-PCR.RESULTS: LINC00511 expression was significantly up-regulated in HCC tissues and cell lines, and its high expression was distinctly associated with nodal metastasis, vascular invasion, and clinical stage. Furthermore, statistical assays revealed that HCC patients with higher LINC00511 expression levels had worse overall survival rates. Importantly, the multivariate analysis confirmed that LINC00511 expression was an independent prognostic factor of the overall survival in patients with HCC. Functionally. the inhibition of LINC00511 significantly suppressed the capability of proliferation, migration, and invasion in HCC cell lines. Bioinformatic tools predicted that miR-424 both targeted the 3'-UTR of LINC00511, which was confirmed using the luciferase reporter assay and RT-PCR.CONCLUSIONS: LINC00511 plays an important role in the malignant progression of HCC via modulation of miR-424.