Role of long non-coding RNA RP11-288L9.1 in systemic lupus erythematosus and underlying mechanism

Chenglei ZHAO; Xingwang ZHAO; Junkai GUO; Juan WANG; Min ZHANG; Lian ZHANG; Yi YOU

doi:10.16016/j.1000-5404.202101010

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Role of long non-coding RNA RP11-288L9.1 in systemic lupus erythematosus and underlying mechanism

Basic Medicine | 更新时间：2026-01-09

- Role of long non-coding RNA RP11-288L9.1 in systemic lupus erythematosus and underlying mechanism
- Journal of Third Military Medical University Vol. 43, Issue 13, Pages: 1204-1211(2021)
- 作者机构：
  
  400038 陆军军医大学(第三军医大学)第一附属医院皮肤科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81673058);the Project of Basic Science and Frontier Technology Research of Chongqing(cstc2017jcyjAX0251)
- DOI：10.16016/j.1000-5404.202101010
  CLC： R392.13;R392.32;R593.24
- Received：03 January 2021，
  
  Revised：2021-02-05，
  
  Published：15 July 2021
- 稿件说明：
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Chenglei ZHAO, Xingwang ZHAO, Junkai GUO, et al. Role of long non-coding RNA RP11-288L9.1 in systemic lupus erythematosus and underlying mechanism[J]. Journal of Third Military Medical University, 2021, 43(13): 1204-1211.
DOI：

Chenglei ZHAO, Xingwang ZHAO, Junkai GUO, et al. Role of long non-coding RNA RP11-288L9.1 in systemic lupus erythematosus and underlying mechanism[J]. Journal of Third Military Medical University, 2021, 43(13): 1204-1211. DOI： 10.16016/j.1000-5404.202101010.

摘要

目的

探讨长链非编码RNA(long non-conding RNA，lncRNA)RP11-288L9.1在系统性红斑狼疮(systemic lupus erythematosus，SLE)中的作用及机制。

方法

通过转录组测序方法(RNA-seq)筛选获得SLE患者外周血单核细胞(peripheral blood mononuclear cell

PBMCs)中差异表达的lncRNAs，采用实时定量PCR(quantitative real-time PCR，qRT-PCR)技术验证8例SLE患者和8例健康对照PBMCs中差异表达的lncRNA的表达水平。运用荧光原位杂交FISH技术检测RP11-288L9.1的细胞定位；设计并构建RP11-288L9.1敲低和过表达重组慢病毒，转染构建RP11-288L9.1敲低和过表达模型，采用qRT-PCR验证其转染效率。分别采用CCK-8和Annexin V-FITC细胞凋亡检测试剂盒检测慢病毒转染后巨噬细胞的增殖和凋亡能力，qRT-PCR检测敲低和高表达RP11-288L9.1后，巨噬细胞相关炎症细胞因子IL-1β、IL-6、IL-4、IL-10、TGF-β1的表达。

结果

通过转录组数据发现6个差异表达的lncRNA(

0.05)。qRT-PCR验证RP11-288L9.1表达显著上调(

0.01)。RP11-288L9.1定位在巨噬细胞胞浆中。过表达RP11-288L9.1可促进巨噬细胞的凋亡并抑制增殖(

0.05)，相关炎症因子IL-1β、IL-6表达显著上升，IL-4、IL-10、TGF-β1表达显著下降(

0.001)；敲低RP11-288L9.1可促进巨噬细胞的增殖并抑制凋亡(

0.05)，相关炎症因子IL-1β、IL-6表达显著下降(

0.01)，IL-4、IL-10、TGF-β1表达显著上升(

0.01)。

结论

RP11-288L9.1在SLE患者PBMCs中高表达，并在巨噬细胞中通过影响炎症细胞因子的合成来调控免疫反应，这可能是SLE发病机制之一。

Abstract

Objective

To investigate the role of long non-coding RNA (lncRNA) RP11-288L9.1 in systemic lupus erythematosus (SLE) and its potential mechanism.

Methods

Transcriptome sequencing (RNA-seq) was used to screen the differentially expressed lncRNAs in peripheral blood mononuclear cells (PBMCs) of SLE patients

and the expression levels of these lncRNAs in 8 pairs of SLE patients and healthy controls were further verified by qRT-PCR. The knockdown as well as over-expression models of RP11-288L9.1 were constructed respectively by transfecting recombinant lentivirus into macrophages

and the transfection efficiency was determined subsequently. The subcellular distribution of RP11-288L9.1 was detected by fluorescence

in situ

hybridization (FISH) technique. Moreover

CCK-8 assay and Annexin V-FITC apoptosis detection kit were applied to examine the proliferation and apoptosis of macrophages in both models

and qRT-PCR was conducted to detect the expression of macrophage-related inflammatory cytokines

IL-1β

IL-6

IL-4

IL-10 and TGF-β1 after the transfection.

Results

Six differentially expressed lncRNAs were found (

0.05)

in which RP11-288L9.1 was significantly up-regulated (

0.01)

and mainly located in the cytoplasm of macrophages. The over-expression of RP11-288L9.1 promoted the apoptosis and inhibited the proliferation of macrophages (

0.05)

increasing the levels of IL-1β and IL-6

and decreasing those of IL-4

IL-10 and TGF-β1 (

0.01). In contrast

the knockdown of RP11-288L9.1 significantly induced the proliferation of macrophages and inhibited the apoptosis (

0.05)

with lowered levels of IL-1β and IL-6 and elevated IL-4

IL-10 and TGF-β1 (

0.01).

Conclusion

RP11-288L9.1 is highly expressed in the PBMCs of SLE patients

and regulates immune response in macrophages by affecting the synthesis of inflammatory cytokines

which may contribute to the occurrence of SLE.

关键词

Keywords

references

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