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

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 (TCG...

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Main Authors: ZHANG Min, LI Min, XIAO Meng
Format: Article
Language:Chinese
Published: Editorial Office of Journal of Army Medical University 2025-07-01
Series:陆军军医大学学报
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Online Access:https://aammt.tmmu.edu.cn/html/202504078.html
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author ZHANG Min
LI Min
XIAO Meng
author_facet ZHANG Min
LI Min
XIAO Meng
author_sort ZHANG Min
collection DOAJ
description 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 assays 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 (P<0.001). The CRC patients with high SNTB1 expression exhibited poorer prognosis when compared with those with low expression level (P<0.05). Moreover, high SNTB1 expression was negatively correlated with immune scores in the tumor microenvironment and immune cell infiltration, especially CD8+ T cells (P<0.05). Furthermore, Knockdown of SNTB1 in HT-29 cells enhanced the cytotoxic activity of CD8+ T cells (P<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 (P<0.001). Transfection with the miR-543 mimic inhibited the expression of SNTB1 in HT-29 cells (P<0.001), while overexpressing SNTB1 counteracted the promotion effect of miR-543 mimics on CD8+ T cell-mediated cytotoxicity (P<0.05). Conclusion‍ ‍MiR-543 activates CD8+ T cells and enhances their cytotoxicity against HT-29 cells by directly targeting SNTB1.
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publisher Editorial Office of Journal of Army Medical University
record_format Article
series 陆军军医大学学报
spelling doaj-art-e62443b6f97942b89a9f9f7317c6d69f2025-07-14T06:03:26ZzhoEditorial Office of Journal of Army Medical University陆军军医大学学报2097-09272025-07-0147131484149310.16016/j.2097-0927.202504078MiR-543/SNTB1 axis modulates immune microenvironment in colorectal cancerZHANG Min0LI Min1XIAO Meng2School of Medicine, Xinyang Hospital of Traditional Chinese Medicine, Xinyang, Henan, ChinaSchool of Medicine, Xinyang Hospital of Traditional Chinese Medicine, Xinyang, Henan, ChinaSchool of Medicine, Xinyang Hospital of Traditional Chinese Medicine, Xinyang, Henan, ChinaObjective‍ ‍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 assays 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 (P<0.001). The CRC patients with high SNTB1 expression exhibited poorer prognosis when compared with those with low expression level (P<0.05). Moreover, high SNTB1 expression was negatively correlated with immune scores in the tumor microenvironment and immune cell infiltration, especially CD8+ T cells (P<0.05). Furthermore, Knockdown of SNTB1 in HT-29 cells enhanced the cytotoxic activity of CD8+ T cells (P<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 (P<0.001). Transfection with the miR-543 mimic inhibited the expression of SNTB1 in HT-29 cells (P<0.001), while overexpressing SNTB1 counteracted the promotion effect of miR-543 mimics on CD8+ T cell-mediated cytotoxicity (P<0.05). Conclusion‍ ‍MiR-543 activates CD8+ T cells and enhances their cytotoxicity against HT-29 cells by directly targeting SNTB1. https://aammt.tmmu.edu.cn/html/202504078.html‍mir-543colorectal cancersntb1tumor immune microenvironment
spellingShingle ZHANG Min
LI Min
XIAO Meng
MiR-543/SNTB1 axis modulates immune microenvironment in colorectal cancer
陆军军医大学学报
‍mir-543
colorectal cancer
sntb1
tumor immune microenvironment
title MiR-543/SNTB1 axis modulates immune microenvironment in colorectal cancer
title_full MiR-543/SNTB1 axis modulates immune microenvironment in colorectal cancer
title_fullStr MiR-543/SNTB1 axis modulates immune microenvironment in colorectal cancer
title_full_unstemmed MiR-543/SNTB1 axis modulates immune microenvironment in colorectal cancer
title_short MiR-543/SNTB1 axis modulates immune microenvironment in colorectal cancer
title_sort mir 543 sntb1 axis modulates immune microenvironment in colorectal cancer
topic ‍mir-543
colorectal cancer
sntb1
tumor immune microenvironment
url https://aammt.tmmu.edu.cn/html/202504078.html
work_keys_str_mv AT zhangmin mir543sntb1axismodulatesimmunemicroenvironmentincolorectalcancer
AT limin mir543sntb1axismodulatesimmunemicroenvironmentincolorectalcancer
AT xiaomeng mir543sntb1axismodulatesimmunemicroenvironmentincolorectalcancer