MiR-543/SNTB1 axis modulates immune microenvironment in colorectal cancer

ZHANG Min; LI Min; XIAO Meng; CHEN Cai; ZHENG Xiaoju; LEI Yuguang

doi:10.16016/j.2097-0927.202504078

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MiR-543/SNTB1 axis modulates immune microenvironment in colorectal cancer

Basic Medicine | 更新时间：2025-07-14

- MiR-543/SNTB1 axis modulates immune microenvironment in colorectal cancer
- Journal of Army Medical University Vol. 47, Issue 13, Pages: 1484-1493(2025)
- 作者机构：
  
  1.信阳职业技术学院：，医学院，河南信阳
  2.信阳职业技术学院：，药学院，河南信阳
  3.信阳市中医院病理科，河南信阳
- 作者简介：
  
  ZHANG Min， E-mail： 470361625@qq.com
- 基金信息：
  
  the Medical Scientific Research Project of Health Commission of Henan Province(WJLX2023248)
- DOI：10.16016/j.2097-0927.202504078
  CLC： R394.3;R730.23;R735.35
- Received：18 April 2025，
  
  Revised：20 June 2025，
  
  Published：15 July 2025
- 稿件说明：
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张敏，李敏，肖猛，等.miR-543/SNTB1轴调控结直肠癌免疫微环境［J］.陆军军医大学学报，2025，47（13）：1484-1493.DOI：10.16016/j.2097-0927.202504078.

ZHANG M，LI M，XIAO M，et al.MiR-543/SNTB1 axis modulates immune microenvironment in colorectal cancer［J］.J Army Med Univ，2025，47（13）：1484-1493.DOI：10.16016/j.2097-0927.202504078.
张敏，李敏，肖猛，等.miR-543/SNTB1轴调控结直肠癌免疫微环境［J］.陆军军医大学学报，2025，47（13）：1484-1493.DOI：10.16016/j.2097-0927.202504078. DOI：

ZHANG M，LI M，XIAO M，et al.MiR-543/SNTB1 axis modulates immune microenvironment in colorectal cancer［J］.J Army Med Univ，2025，47（13）：1484-1493.DOI：10.16016/j.2097-0927.202504078. DOI：

摘要

目的

探讨miR-543/互养蛋白β1（syntrophin beta 1，SNTB1）轴在结直肠癌（colorectal cancer，CRC）中的临床意义及其对免疫微环境的影响。

方法

收集癌症基因组图谱（the Cancer Genome Atlas，TCGA）、基因型组织表达（Genotype-Tissue Ex

pression，GTEx）、人类蛋白质图谱（Human Protein Atlas，HPA）等公开数据对CRC组织中

SNTB1

的表达进行分析，并通过Kaplan-Meier生存分析、单因素Cox回归分析及相关性分析评估

SNTB1

在CRC患者中的预后价值及其与免疫微环境的关系。在线数据库结合CRC细胞HT-29荧光活性实验检测miR-543与SNTB1的靶向关系。CRC细胞HT-29经过相应处理后（转染si-SNTB1、miR-543 mimics或/和

SNTB1

过表达质粒）与CD8

T细胞构建体外共培养体系，分别采用RT-qPCR、Western blot、流式细胞术、ELISA以及乳酸脱氢酶（lactate dehydrogenase，LDH）释放实验检测

miR-543

、

SNTB1

的表达以及CD8

T细胞的活性及细胞毒性。

结果

对公共数据库的分析显示

SNTB1

在CRC中的表达显著高于正常组织（

0.001）；相较于

SNTB1

低表达组，

SNTB1

高表达的患者预后较差（

0.05）。SNTB1高表达与CRC肿瘤微环境免疫评分以及CD8

T细胞等免疫细胞的浸润呈负相关关系（

0.05），且在HT-29细胞中敲减

SNTB1

可增强CD8

T细胞的杀伤力（

0.01）。在线数据库结合细胞实验证实了miR-543和SNTB1的靶向结合关系，同时miR-543在CRC中表达降低（

0.001）。转染miR-543 mimic可抑制HT-29细胞中SNTB1的表达（

0.001），而过表达

SNTB1

可逆转miR-543 mimic对CD8

T细胞体外杀伤能力的促进效应（

0.05）。

结论

miR-543可通过与SNTB1的靶向结合促进CD8

T细胞的活化并增强其对HT-29细胞的杀伤力。

Abstract

‍Objective‍　‍To investigate the clinical significance of the miR-543/syntrophin beta 1 (SNTB1) axis in colorectal cancer (CRC) and its influence on the tumor immune microenvironment. Methods‍　‍The expression of

SNTB1

in CRC tissues was analyzed using public data

such as

The Cancer Genome Atlas (TCGA)

Genotype-Tissue Expression (GTEx)

and Human Protein Atlas (HPA). Then Kaplan-Meier survival analysis

univariate Cox regression analysis and correlation analysis were performed to evaluate the prognostic value of

SNTB1

and its relationship with immune microenvironment in CRC. The targeting relationship between

miR-543

and

SNTB1

was confirmed through online databases and fluorescence assay

s in HT-29 cells. For

in vitro

experiments

after transfecting si-SNTB1

miR-543 mimics and/or

SNTB1

overexpression plasmids

HT-29 cells were co-cultured with CD8

T cells

the expression of miR543 and

SNTB1

and the viability and cytotoxicity of CD8

T cells were assessed with qRT-PCR

Western blotting

flow cytometry

ELISA

and lactate dehydrogenase (LDH) release assay. Results‍　‍Analysis of public databases revealed significantly higher expression of

SNTB1

in CRC tissues than normal tissues (

0.001). The CRC patients with high

SNTB1

expression exhibited poorer prognosis when compared with those with low expression level (

0.05). Moreover

high

SNTB1

expression was negatively correlated with immune scores in the tumor microenvironment and immune cell infiltration

especially CD8

T cells (

0.05). Furthermore

Knockdown of

SNTB1

in HT-29 cells enhanced the cytotoxic activity of CD8

T cells (

0.01). Online database and

in vitro

experiments confirmed that miR-543 targets

SNTB1

while the expression of miR-543 was decreased in colorectal cancer (

0.001). Transfection with the miR-543 mimic inhibited the expression of

SNTB1

in HT-29 cells (

0.001)

while overexpressing

SNTB1

counteracted the promotion effect of miR-543 mimics on CD8

T cell-mediated cytotoxicity (

0.05). Conclusion‍　‍MiR-543 activates CD8

T cells and enhances their cytotoxicity against HT-29 cells by directly targeting SNTB1.

关键词

Keywords

references

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