miR-382-5p通过Akt/mTOR信号通路影响乳腺癌肿瘤相关巨噬细胞极化

周华; 王园园; 林子晶; 明佳

doi:10.16016/j.1000-5404.202102001

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miR-382-5p通过Akt/mTOR信号通路影响乳腺癌肿瘤相关巨噬细胞极化

基础医学 | 更新时间：2026-01-09

- miR-382-5p通过Akt/mTOR信号通路影响乳腺癌肿瘤相关巨噬细胞极化
- miR-382-5p affects polarization of tumor-associated macrophages in breast cancer through Akt/mTOR signaling pathway
- 第三军医大学学报 2021年43卷第14期页码：1358-1365
- 作者机构：
  
  400010 重庆，重庆医科大学附属第二医院乳甲外科
- 作者简介：
  
  [ 明佳，E-mail: mjia1001@sina.com MING Jia, E-mail: mjia1001@sina.com
- 基金信息：
  
  重庆医科大学附属第二医院“宽仁英才”骨干人才项目(KY2019G016);重庆技术创新与应用示范(社会民生类)一般项目(CSTC2018jscx-msybx0020);重庆市渝中区科技计划项目(20160104)
- DOI：10.16016/j.1000-5404.202102001
  中图分类号： R394.3;R730.23;R737.9
- 收稿：2021-02-01，
  
  修回：2021-04-27，
  
  纸质出版：2021-07-30
- 稿件说明：
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周华, 王园园, 林子晶, 等. miR-382-5p通过Akt/mTOR信号通路影响乳腺癌肿瘤相关巨噬细胞极化[J]. 第三军医大学学报, 2021,43(14):1358-1365.

Hua ZHOU, Yuanyuan WANG, Zijing LIN, et al. miR-382-5p affects polarization of tumor-associated macrophages in breast cancer through Akt/mTOR signaling pathway[J]. Journal of Third Military Medical University, 2021, 43(14): 1358-1365.
周华, 王园园, 林子晶, 等. miR-382-5p通过Akt/mTOR信号通路影响乳腺癌肿瘤相关巨噬细胞极化[J]. 第三军医大学学报, 2021,43(14):1358-1365. DOI： 10.16016/j.1000-5404.202102001.

Hua ZHOU, Yuanyuan WANG, Zijing LIN, et al. miR-382-5p affects polarization of tumor-associated macrophages in breast cancer through Akt/mTOR signaling pathway[J]. Journal of Third Military Medical University, 2021, 43(14): 1358-1365. DOI： 10.16016/j.1000-5404.202102001.

摘要

目的

探讨乳腺癌肿瘤相关巨噬细胞(tumor-associated macrophages

TAMs)中miR-382-5p的表达对巨噬细胞极化表型以及乳腺癌生物学特性的影响和可能机制。

方法

收集2018-2020年本院25例临床乳腺癌患者的肿瘤相关巨噬细胞及配对癌旁组织巨噬细胞，用qRT-PCR检测miR-382-5p的表达；利用miR-382-5p过表达慢病毒转染小鼠腹腔巨噬细胞(mouse peritoneal macrophages，PMs)，qRT-PCR、Western blot检测巨噬细胞的M1/M2极化指标(iNOS、TNF-α、Arg-1、IL-10等)、miR-382-5p以及Akt/mTOR信号通路变化，采用流式细胞仪检测CD86、CD206的表达；将4T1细胞与TAMs、过表达miR-382-5p的TAMs共培养或培养上清液处理后，CCK-8实验检测4T1细胞的增殖能力，Transwell实验检测4T1细胞的侵袭能力，细胞划痕实验检测4T1细胞的迁移能力。

结果

25例临床标本的乳腺癌TAMs的miR-382-5p表达水平较配对癌旁组织巨噬细胞明显降低(

0.05)；与对照组比较，过表达miR-382-5p的TAMs的M1型极化标记物(iNOS、TNF-α、CD86等)的表达水平升高，M2型极化标记物(Arg-1、IL-10、CD206)的表达水平降低(

0.05)；Akt/mTOR信号通路相关蛋白磷酸化水平明显降低(

0.05)；4T1细胞的增殖、侵袭、迁移能力被抑制(

0.05)。

结论

miR-382-5p可能通过改变乳腺癌TAMs的极化状态影响乳腺癌细胞的侵袭、迁移等过程；其机制可能与miR-382-5p介导Akt/mTOR信号通路调节巨噬细胞极化相关。

Abstract

Objective

To investigate the effects of microRNA-382-5p (miR-382-5p) expression in breast cancer tumor-associated macrophages (TAMs) on the polarization phenotype of macrophages as well as the biological characteristics of breast cancer

and to explore its possible mechanism.

Methods

Breast cancer TAMs and their paring macrophages from adjacent tissues of 25 breast cancer patients treated in our hospital between 2018 and 2020 were collected

and the expression of miR-382-5p was detected by qRT-PCR. Mouse peritoneal macrophages (PMs) were transfected with miR-382-5p over-expressed lentivirus. The changes of M1/M2 polarization indicators (iNOS

TNF-α

Arg-1

IL-10

etc.) and the expression of miR-382-5p and Akt/mTOR signaling pathway were determined by qRT-PCR and Western blotting

and the expression of CD86 and CD206 were tested using flow cytometry. After the 4T1 mouse breast cancer cells were co-cultured with TAMs and TAMs overexpressing miR-382-5p

respectively

or treated with the corresponding supernatants

the proliferative capacity of 4T1 cells was subsequently tested by CCK-8 assay

the invasion ability and the migration ability of 4T1 cells were observed using Transwell assay and cell scratch assay

respectively.

Results

The level of miR-382-5p in breast cancer TAMs was significantly lower than that in macrophages of pairing adjacent tissues (

0.05). Compared with the control group

the levels of M1-phenotype polarization markers (iNOS

TNF-α

CD86

etc.) were increased

while those of M2 indicators (Arg-1

IL-10

CD206) were decreased in the miR-382-5p overexpressed group (

0.05)

and the phosphorylation levels of the proteins related to Akt/mTOR signaling pathway were reduced (

0.05). In addition

the abilities of proliferation

invasion and migration of 4T1 cells were all inhibited in the miR-382-5p overexpressed group as compared with the TAMs group (

0.05).

Conclusion

miR-382-5p may possibly play a vital role in the invasion and migration processes of breast cancer cells by affecting the polarization phenotypes of TAMs

and the mechanism may be associated with miR-382-5p mediated Akt/mTOR signaling pathway in the regulation of macrophage polarization.

关键词

Keywords

references

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