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长链非编码 RNA CRNDE 作为骨肉瘤的诊断和预后生物标志物发挥作用,并且通过抑制 miR-335-3p 促进其进展。

Long noncoding RNA CRNDE functions as a diagnostic and prognostic biomarker in osteosarcoma, as well as promotes its progression via inhibition of miR-335-3p.

机构信息

Department of Laboratory, Zhengzhou Orthopedic Hospital, Zhengzhou, China.

Department of Orthopedic Surgery, Zhumadian Central Hospital, Zhumadian, China.

出版信息

J Biochem Mol Toxicol. 2021 May;35(5):e22734. doi: 10.1002/jbt.22734. Epub 2021 Feb 1.

Abstract

BACKGROUND

This study was performed to evaluate the diagnostic and prognostic value, as well as the role of long-chain noncoding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) in osteosarcoma (OS).

MATERIALS AND METHODS

A quantitative real-time polymerase chain reaction assay was to determine lncRNA CRNDE and microRNA-335-3p (miR-335-3p) expressions. The Kaplan-Meier analysis was to analyze the relationship between lncRNA CRNDE expression and survival in patients with OS. Receiver operating characteristic curves were to evaluate the diagnostic value of lncRNA CRNDE in OS. Bioinformatics analysis and luciferase reporter assays were used to predict and confirm the relationship between lncRNA CRNDE and miR-335-3p. Cell counting Kit-8 and transwell migration assays assessed the role of lncRNA CRNDE and miR-335-3p in OS cells.

RESULTS

lncRNA CRNDE expression was upregulated and miR-355-3p expression was downregulated in OS. In patients with OS, low lncRNA CRNDE expression demonstrated higher overall survival, whereas high lncRNA CRNDE expression was an independent poor prognostic factor. Furthermore, increased lncRNA CRNDE expression was associated with distant metastasis and the tumor-node-metastasis stage in patients with OS, which can be considered as an independent diagnostic biomarker in OS. We revealed that miR-335-3p was the target of lncRNA CRNDE. It also demonstrated that knockdown of lncRNA CRNDE inhibited OS cell proliferation, migration, and invasion, and inhibition of miR-355-3p promoted this effect. Finally, miR-335-3p partially mediated the stimulatory effects of lncRNA CRNDE in OS.

CONCLUSION

We demonstrated that lncRNA CRNDE is a potential diagnostic and prognostic biomarker for OS, and the lncRNA CRNDE/miR-335-3p axis participates in OS progression.

摘要

背景

本研究旨在评估长链非编码 RNA(lncRNA)结直肠肿瘤差异表达(CRNDE)在骨肉瘤(OS)中的诊断和预后价值及其作用。

材料和方法

采用实时定量聚合酶链反应检测 lncRNA CRNDE 和 microRNA-335-3p(miR-335-3p)的表达。Kaplan-Meier 分析评估 lncRNA CRNDE 表达与 OS 患者生存的关系。受试者工作特征曲线评估 lncRNA CRNDE 在 OS 中的诊断价值。生物信息学分析和荧光素酶报告基因实验用于预测和验证 lncRNA CRNDE 与 miR-335-3p 的关系。细胞计数试剂盒-8 和 Transwell 迁移实验评估 lncRNA CRNDE 和 miR-335-3p 在 OS 细胞中的作用。

结果

OS 中 lncRNA CRNDE 表达上调,miR-355-3p 表达下调。在 OS 患者中,低 lncRNA CRNDE 表达提示总生存率更高,而高 lncRNA CRNDE 表达是独立的不良预后因素。此外,lncRNA CRNDE 表达增加与 OS 患者的远处转移和肿瘤-淋巴结-转移分期相关,可作为 OS 的独立诊断生物标志物。我们揭示了 miR-335-3p 是 lncRNA CRNDE 的靶基因。还表明,lncRNA CRNDE 敲低抑制 OS 细胞增殖、迁移和侵袭,而抑制 miR-355-3p 则促进了这种作用。最后,miR-335-3p 部分介导了 lncRNA CRNDE 在 OS 中的刺激作用。

结论

我们证明 lncRNA CRNDE 是 OS 的潜在诊断和预后生物标志物,lncRNA CRNDE/miR-335-3p 轴参与 OS 进展。

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