Role of long non-coding RNA ENST 933 in breast cancer and its underlying mechanism

Yumei DENG; Junxia CHEN

doi:10.16016/j.2097-0927.202401022

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Role of long non-coding RNA ENST 933 in breast cancer and its underlying mechanism

Basic Medicine | 更新时间：2026-01-09

- Role of long non-coding RNA ENST 933 in breast cancer and its underlying mechanism
- Journal of Army Medical University Vol. 46, Issue 14, Pages: 1676-1694(2024)
- 作者机构：
  
  400016 重庆，重庆医科大学分子医学与肿瘤研究中心
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(82173170)
- DOI：10.16016/j.2097-0927.202401022
  CLC： R394.3;R730.23;R737.9
- Received：05 January 2024，
  
  Revised：2024-03-09，
  
  Published：30 July 2024
- 稿件说明：
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Yumei DENG, Junxia CHEN. Role of long non-coding RNA ENST 933 in breast cancer and its underlying mechanism[J]. Journal of Army Medical University, 2024, 46(14): 1676-1694.
DOI：

Yumei DENG, Junxia CHEN. Role of long non-coding RNA ENST 933 in breast cancer and its underlying mechanism[J]. Journal of Army Medical University, 2024, 46(14): 1676-1694. DOI： 10.16016/j.2097-0927.202401022.

摘要

目的

探讨长链非编码RNA ENST00000579933(简称lncRNA ENST 933)对乳腺癌(breast cancer，BC)发展的调控机制。

方法

通过实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction，RT-qPCR)检测lncRNA ENST 933在BC组织和BC细胞系(MCF-7、MDA-MB-231、MDA-MB-453)中的表达；运用细胞计数试剂盒-8(cell counting kit-8，CCK-8)、克隆形成、EdU、Transwell、流式细胞仪、蛋白质印迹法(Western blot)、体内移植瘤实验检测lncRNA ENST 933和miR-588在BC细胞增殖、迁移、侵袭与周期中的作用；采用双荧光素酶报告基因、RNA免疫共沉淀实验、RT-qPCR、Western blot和挽救实验来评估lncRNA ENST 933、miR-588、真核起始因子6(eukaryotic initiation factor 6，EIF6)之间的互相作用。

结果

lncRNA ENST 933在BC组织和BC细胞系中表达均显著上调(

＜0.05)，过表达lncRNA ENST 933能够提升BC细胞增殖、迁移与侵袭能力，促进移植瘤生长，而敲低lncRNA ENST 933表达后BC的发展受到抑制，并导致细胞周期阻滞(

＜0.05)。miR-588在BC组织中表达明显下调，过表达miR-588可抑制BC细胞的增殖、迁移与侵袭(

＜0.05)。挽救实验结果表明lncRNA ENST 933可通过与miR-588进行竞争性结合，从而促进靶基因EIF6的表达。Western blot结果显示miR-588降低了AKT和mTOR的磷酸化水平(

＜0.05)。

结论

lncRNA ENST 933可通过调控miR-588/EIF6轴促进BC的进展。

Abstract

Objective

To investigate the regulatory mechanism of long non-coding RNA (lncRNA) ENST00000579933 (hereinafter referred to as lncRNA ENST 933) on the development of breast cancer (BC).

Methods

The expression level of lncRNA ENST 933 in BC tissues as well as in BC cell lines (MCF-7

MDA-MB-231

MDA-MB-453) was detected by fluorescence-based real-time quantitative polymerase chain reaction RT-qPCR. The effects of lncRNA ENST 933 and miR-588 on the proliferation

migration

invasion and cell cycle in BC were determined using CCK-8 assay

clone formation assay

EdU

Transwell assay

flow cytometry

Western blotting and

in vivo

transplantation tumor assay. Finally

dual luciferase reporter gene

RNA immunoprecipitation assay

RT-qPCR

Western blotting and rescue assay were used to evaluate the interactions among lncRNA ENST 933

miR-588

and eukaryotic initiation factor 6 (EIF6).

Results

The expression of lncRNA ENST 933 was up-regulated in both BC tissues and BC cell lines (

0.05). Overexpression of lncRNA ENST 933 could enhance the proliferation

migration and invasion abilities of BC cells and promote

the growth of transplanted tumors

while knockdown of lncRNA ENST 933 resulted in inhibited development of BC and arrested cell cycle (

0.05). The expression of miR-588 was obviously down-regulated in BC tissues

and its overexpression inhibited cell proliferation

migration and invasion abilities in the BC cells (

0.05). Moreover

the results of rescue assay indicated that lncRNA ENST 933 promoted the expression of target gene EIF6 by competitively binding with miR-588. Western blotting revealed that miR-588 decreased the phosphorylation of AKT and mTOR (

0.05).

Conclusion

lncRNA ENST 933 promotes the progression of BC by modulating the miR-588/EIF6 axis.

关键词

Keywords

references

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