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长非编码 RNA LINP1 通过影响 Wnt/β-catenin 信号通路诱导肾母细胞瘤的发生。

Long non-coding RNA LINP1 induces tumorigenesis of Wilms' tumor by affecting Wnt/β-catenin signaling pathway.

机构信息

Department of Pediatrics, Jining No. 1 People's Hospital, Jining, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Jul;23(13):5691-5698. doi: 10.26355/eurrev_201907_18306.

DOI:10.26355/eurrev_201907_18306
PMID:31298321
Abstract

OBJECTIVE

Recent studies have discovered that long non-coding RNAs (lncRNAs) play an important role in the development of malignant tumors. The aim of this work was to investigate the exact role of lncRNA LINP1 in the development of Wilms' tumor and to explore the possible underlying mechanism.

PATIENTS AND METHODS

The expression of lncRNA in non-homologous end joining pathway 1 (LINP1) in tissue samples of Wilms' tumor was detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). The relationship between the expression of lung cancer associated transcript 1 (LUCAT1) and patients' overall survival time was analyzed. Subsequent functional experiments were conducted to identify the changes in biological behaviors of Wilms' tumor cells after the gain or loss of LINP1. Moreover, the underlying mechanism of LINP1 function was explored.

RESULTS

QRT-PCR results showed that LINP1 expression level in Wilms' tumor tissues was significantly higher than that of adjacent tissues. LINP1 expression was negatively associated with the overall survival time of patients with Wilms' tumor. Cell growth ability was markedly inhibited and promoted after down-regulation and overexpression of LINP1 in vitro, respectively. Moreover, after the loss and gain of LINP1 in vitro, cell migration and invasion abilities were remarkably repressed and promoted, respectively. Furthermore, the loss of LINP1 in vitro could significantly decrease the expressions of targeted proteins in the Wnt/β-catenin signaling pathway. However, the expressions of targeted proteins in the Wnt/β-catenin signaling pathway were remarkably up-regulated after over-expression of LINP1.

CONCLUSIONS

LINP1 could enhance cell metastasis and proliferation via inducing the Wnt/β-catenin signaling pathway. Our findings might provide a new prospect for the diagnosis and therapy of Wilms' tumor.

摘要

目的

最近的研究发现,长链非编码 RNA(lncRNA)在恶性肿瘤的发展中发挥着重要作用。本研究旨在探讨 lncRNA LINP1 在威尔姆斯瘤(Wilms' tumor)发生发展中的具体作用,并探索可能的潜在机制。

患者与方法

采用实时定量聚合酶链反应(RT-qPCR)检测非同源末端连接通路 1(LINP1)在威尔姆斯瘤组织样本中的表达情况。分析肺癌相关转录本 1(LUCAT1)的表达与患者总生存时间的关系。随后进行功能实验,以鉴定 LINP1 获得或缺失后威尔姆斯瘤细胞生物学行为的变化。此外,还探讨了 LINP1 功能的潜在机制。

结果

qRT-PCR 结果显示,LINP1 在威尔姆斯瘤组织中的表达水平明显高于相邻组织。LINP1 的表达与威尔姆斯瘤患者的总生存时间呈负相关。体外下调和过表达 LINP1 后,细胞生长能力显著受到抑制和促进。此外,体外失活和过表达 LINP1 后,细胞迁移和侵袭能力显著受到抑制和促进。此外,体外 LINP1 失活可显著降低 Wnt/β-catenin 信号通路中靶蛋白的表达。然而,过表达 LINP1 后,Wnt/β-catenin 信号通路中靶蛋白的表达明显上调。

结论

LINP1 可通过诱导 Wnt/β-catenin 信号通路增强细胞转移和增殖。我们的研究结果可能为威尔姆斯瘤的诊断和治疗提供新的前景。

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