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长链非编码 RNA SNHG12 的表达增加预示着鼻咽癌预后不良,并通过调节 Notch 信号通路调节细胞增殖和转移。

Increased expression of lncRNA SNHG12 predicts a poor prognosis of nasopharyngeal carcinoma and regulates cell proliferation and metastasis by modulating Notch signal pathway.

出版信息

Cancer Biomark. 2018;23(4):603-613. doi: 10.3233/CBM-181873.

Abstract

BACKGROUND

Small nucleolar RNA host gene 12 (SNHG12) has been shown to be a long noncoding RNA (lncRNA) that facilitates the progression of a number of malignancies. However, the expression pattern and biological function of SNHG12 in nasopharyngeal carcinoma (NPC) have not been investigated.

OBJECTIVE

The aim of our study is to investigate the expression, clinical significance and function of SNHG12 in NPC.

METHODS

RT-PCR was used to detect the expression of SNHG12 in NPC cell lines and primary tumor tissues. The correlation of SNHG12 with clinicopathological features and patient prognosis was analyzed. The biologic functions of SNHG12 in NPC were explored by MTT assay, colony formation assay, wound healing assays, transwell assay and flow cytometric analysis in vitro. The expression of EMT markers and Notch signal pathway markers were determined by western blotting.

RESULTS

The expression levels of SNHG12 were up-regulated in both NPC tissues and cell lines. High SNHG12 expression was significantly associated with clinical stage, grade and poor prognosis. Multivariate analysis demonstrated that high lncRNA SNHG12 expression was an independent poor prognostic factor for NPC patients. Functionally, knockdown of SNHG12 suppressed NPC cells proliferation, migration and invasion. Mechanistic investigations showed that knockdown of SNHG12 suppressed the activation of EMT and Notch-1 signal pathway.

CONCLUSIONS

Our data suggest that SNHG12 promotes the progression of NPC and is a potential therapeutic target for NPC intervention.

摘要

背景

小核仁 RNA 宿主基因 12(SNHG12)已被证实为一种长非编码 RNA(lncRNA),可促进多种恶性肿瘤的进展。然而,SNHG12 在鼻咽癌(NPC)中的表达模式和生物学功能尚未得到研究。

目的

本研究旨在探讨 SNHG12 在 NPC 中的表达、临床意义和功能。

方法

采用 RT-PCR 检测 NPC 细胞系和原发肿瘤组织中 SNHG12 的表达。分析 SNHG12 与临床病理特征和患者预后的相关性。通过 MTT assay、集落形成 assay、划痕愈合 assay、transwell assay 和流式细胞术分析体外 NPC 中 SNHG12 的生物学功能。通过 Western blot 检测 EMT 标记物和 Notch 信号通路标记物的表达。

结果

SNHG12 在 NPC 组织和细胞系中表达上调。高 SNHG12 表达与临床分期、分级和预后不良显著相关。多因素分析表明,高 lncRNA SNHG12 表达是 NPC 患者的独立不良预后因素。功能上,敲低 SNHG12 抑制 NPC 细胞增殖、迁移和侵袭。机制研究表明,敲低 SNHG12 抑制 EMT 和 Notch-1 信号通路的激活。

结论

我们的数据表明,SNHG12 促进 NPC 的进展,是 NPC 干预的潜在治疗靶点。

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