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长非编码 RNA FOXP4-AS1 作为一个不利的预后因素,调节鼻咽癌的增殖和凋亡。

Long non-coding RNA FOXP4-AS1 acts as an adverse prognostic factor and regulates proliferation and apoptosis in nasopharyngeal carcinoma.

机构信息

Department of ENT of The Affiliated Traditional Chinese Medical Hospital of Southwest Medical University, Luzhou City, Sichuan Province, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Aug;24(15):8008-8016. doi: 10.26355/eurrev_202008_22484.

Abstract

OBJECTIVE

Nasopharyngeal carcinoma (NPC) is one of the most common malignancies worldwide. In The Cancer Genome Atlas (TCGA) database, the expression level of lncRNA forkhead box P4 antisense RNA 1 (FOXP4-AS1) is higher in NPC samples than in normal samples.

PATIENTS AND METHODS

Quantitative Real-time PCR and Western blotting were performed to detect the expression level of RNA and protein. Luciferase reporter assay ran to test the interactions between FOXP4-AS1 and miR-423-5p and STMN1. Subcellular fractionation assay was used to determine the subcellular localization of FOXP4-AS1. The tumor-promotion functions of FOXP4-AS1 were determined by both in vitro and in vivo assays.

RESULTS

The expression of FOXP4-AS1 was up-regulated in 80 cases with NPC, and these patients with a poor prognosis. Functionally, high expression of FOXP4-AS1 in NPC was connected with promoted cell proliferation and inhibited apoptosis. Moreover, FOXP4-AS1 is located in the cytoplasm of CNE1 (NPC cell lines). Mechanistically, FOXP4-AS1 up-regulated STMN1 on post-transcriptional regulation by means of miR-423-5p.

CONCLUSIONS

Our present study demonstrated that high expression of FOXP4-AS1 in NPC portended poor outcomes. FOXP4-AS1upregulated STMN1 by interacting with miR-423-5p as a competing endogenous RNA (ceRNA) to promote NPC progression.

摘要

目的

鼻咽癌(NPC)是全球最常见的恶性肿瘤之一。在癌症基因组图谱(TCGA)数据库中,NPC 样本中长链非编码 RNA 叉头框 P4 反义 RNA 1(FOXP4-AS1)的表达水平高于正常样本。

患者和方法

采用定量实时 PCR 和 Western blot 检测 RNA 和蛋白的表达水平。进行荧光素酶报告基因实验以检验 FOXP4-AS1 与 miR-423-5p 和 STMN1 之间的相互作用。采用亚细胞分离实验确定 FOXP4-AS1 的亚细胞定位。通过体外和体内实验来确定 FOXP4-AS1 的肿瘤促进功能。

结果

在 80 例 NPC 患者中,FOXP4-AS1 的表达上调,这些患者预后不良。功能上,NPC 中 FOXP4-AS1 的高表达与促进细胞增殖和抑制细胞凋亡有关。此外,FOXP4-AS1 位于 CNE1(NPC 细胞系)的细胞质中。从机制上讲,FOXP4-AS1 通过 miR-423-5p 对 STMN1 进行转录后调控而上调。

结论

本研究表明,NPC 中 FOXP4-AS1 的高表达预示着不良预后。FOXP4-AS1 通过与 miR-423-5p 相互作用作为竞争性内源 RNA(ceRNA)上调 STMN1,从而促进 NPC 的进展。

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