长链非编码 RNA LINC00511 的增加与肝癌的不良预后相关，并通过调节 miR-424 促进细胞增殖和转移。
Increased long noncoding RNA LINC00511 is correlated with poor prognosis and contributes to cell proliferation and metastasis by modulating miR-424 in hepatocellular carcinoma.
机构信息
Health Management Center, Department of Infectious Diseases, and Department of Ophthalmology; The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Apr;23(8):3291-3301. doi: 10.26355/eurrev_201904_17691.
OBJECTIVE
Long noncoding RNAs (lncRNAs) 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 lncRNA, 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 ceRNAs 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.
目的
长链非编码 RNA（lncRNA）在人肝细胞癌（HCC）中异常表达，并与 HCC 的进展相关。lncRNA LINC00511（LINC00511）已被证实在几种肿瘤中作为肿瘤促进因子发挥作用。然而，作为一种新的 lncRNA，LINC00511 的具体作用在很大程度上仍然不清楚。在本研究中，我们旨在评估 LINC00511 在 HCC 行为中的作用，并阐明其发生的机制。
方法
通过 qRT-PCR 评估 LINC00511 在 HCC 组织和细胞系中的表达。通过多种统计方法确定 LINC00511 表达与 HCC 患者临床病理参数和预后的相关性。CCK-8 测定、集落形成测定、流式细胞术细胞周期、凋亡测定、EdU 测定、划痕愈合测定和 Transwell 测定用于研究 LINC00511 对体外恶性表型的作用。通过生物信息学分析、双荧光素酶报告基因测定和 RT-PCR 确定 ceRNA 的潜在机制。
结果
LINC00511 的表达在 HCC 组织和细胞系中显著上调，其高表达与淋巴结转移、血管浸润和临床分期明显相关。此外，统计分析表明，LINC00511 表达水平较高的 HCC 患者总生存率较低。重要的是，多变量分析证实 LINC00511 表达是 HCC 患者总生存率的独立预后因素。功能上，抑制 LINC00511 显著抑制了 HCC 细胞系的增殖、迁移和侵袭能力。生物信息学工具预测 miR-424 靶向 LINC00511 的 3'-UTR，这通过荧光素酶报告基因测定和 RT-PCR 得到证实。
结论
LINC00511 通过调节 miR-424 在 HCC 的恶性进展中发挥重要作用。
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