Department of ENT of The Affiliated Traditional Chinese Medical Hospital of Southwest Medical University, Luzhou City, Sichuan Province, China.
Eur Rev Med Pharmacol Sci. 2020 Aug;24(15):8008-8016. doi: 10.26355/eurrev_202008_22484.
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.
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.
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.
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.
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。
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。
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。
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。