长链非编码RNA FOXP4-AS1通过调控miR-136-5p/CBX4轴参与宫颈癌进展。

LncRNA FOXP4-AS1 Is Involved in Cervical Cancer Progression via Regulating miR-136-5p/CBX4 Axis.

作者信息

Zhao Juan, Yang Ting, Li Long

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Mar 19;13:2347-2355. doi: 10.2147/OTT.S241818. eCollection 2020.

INTRODUCTION

Cervical cancer (CC) is a major health threat to women worldwide. Long non-coding RNA (lncRNA) has been reported to play crucial roles in regulating carcinogenesis, including CC.

METHODS

In this work, levels of lncRNA forkhead box P4 antisense RNA 1 (FOXP4-AS1) in CC cell lines and normal cell lines were analyzed with quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) method. Effects of FOXP4-AS1 on CC cellular behaviors including proliferation, migration, and invasion were explored. Bioinformatic prediction tools and luciferase activity reporter assay were conducted to explore the downstream molecules for FOXP4-AS1.

RESULTS

We found FOXP4-AS1 expression was significantly higher in CC cell lines than in normal cell line. Functionally, force FOXP4-AS1 expression increased CC cell proliferation, migration, and invasion, while FOXP4-AS1 knockdown caused opposite effects. Mechanistically, we found FOXP4-AS1 acts as competing endogenous RNA (ceRNA) for microRNA-136-5p (miR-136-5p) to regulate chromobox 4 (CBX4) expression.

DISCUSSION

These findings indicated FOXP4-AS1 plays an oncogenic role in CC, which may provide novel therapeutic biomarker against CC.

引言

宫颈癌（CC）是全球女性面临的主要健康威胁。据报道，长链非编码RNA（lncRNA）在包括CC在内的肿瘤发生调控中发挥关键作用。

方法

在本研究中，采用定量实时聚合酶链反应（qRT-PCR）方法分析了CC细胞系和正常细胞系中lncRNA叉头框P4反义RNA 1（FOXP4-AS1）的水平。探讨了FOXP4-AS1对CC细胞增殖、迁移和侵袭等细胞行为的影响。利用生物信息学预测工具和荧光素酶活性报告基因检测来探索FOXP4-AS1的下游分子。

结果

我们发现CC细胞系中FOXP4-AS1的表达明显高于正常细胞系。在功能上，强制表达FOXP4-AS1可增加CC细胞的增殖、迁移和侵袭，而敲低FOXP4-AS1则产生相反的效果。机制上，我们发现FOXP4-AS1作为微小RNA-136-5p（miR-136-5p）的竞争性内源RNA（ceRNA）来调节染色体框蛋白4（CBX4）的表达。