Veillonella parvula promotes the proliferation of lung adenocarcinoma through the nucleotide oligomerization domain 2/cellular communication network factor 4/nuclear factor kappa B pathway

Abstract Enrichment of Veillonella parvula in the lung microbiota is strongly associated with non-small cell lung cancer (NSCLC) and induces the progression of lung adenocarcinoma in vivo, but its actual role and mechanism remain unexplored. This study analyzed the correlation between NSCLC and V. p...

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Main Authors: Wen Zeng, Yuhuan Wang, Zhe Wang, Mengge Yu, Kang Liu, Chengzhu Zhao, Yiyun Pan, Shudong Ma
Format: Article
Language:English
Published: Springer 2023-07-01
Series:Discover Oncology
Subjects:
Online Access:https://doi.org/10.1007/s12672-023-00748-6
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author Wen Zeng
Yuhuan Wang
Zhe Wang
Mengge Yu
Kang Liu
Chengzhu Zhao
Yiyun Pan
Shudong Ma
author_facet Wen Zeng
Yuhuan Wang
Zhe Wang
Mengge Yu
Kang Liu
Chengzhu Zhao
Yiyun Pan
Shudong Ma
author_sort Wen Zeng
collection DOAJ
description Abstract Enrichment of Veillonella parvula in the lung microbiota is strongly associated with non-small cell lung cancer (NSCLC) and induces the progression of lung adenocarcinoma in vivo, but its actual role and mechanism remain unexplored. This study analyzed the correlation between NSCLC and V. parvula abundance based on 16 s rRNA sequencing results. The effects of V. parvula on the progression of lung adenocarcinoma were observed in vivo and in vitro using a C57 bl/6j mouse tumor-bearing model, a bacterial cell co-culture model, combined with transcriptome sequencing, and a TCGA database to explore and validate the growth promotion of lung adenocarcinoma by V. parvula and its molecular mechanism. 16 s rRNA sequencing revealed that V. parvula was significantly enriched in lung adenocarcinoma. In vivo, V. parvula promoted the growth of lung adenocarcinoma in mice by suppressing the infiltration of tumor-associated T lymphocytes and peripheral T lymphocytes. It showed a higher affinity for lung adenocarcinoma in vitro and promoted lung adenocarcinoma cell proliferation through adhesion or intracellular invasion. Further analysis of differential gene expression and KEGG enrichment by transcriptome sequencing revealed that V. parvula induced CCN4 expression and activated NOD-like receptor and NF-κB signaling pathway in lung adenocarcinoma cells. Further analysis clarified that V. parvula promoted activation of the NF-κB pathway via Nod2/CCN4 signaling, which promoted lung adenocarcinoma cell proliferation. Thus, V. parvula mediates activation of the Nod2/CCN4/NF-κB signaling pathway to promote non-small cell lung adenocarcinoma progression, thereby providing a potential target for diagnosing and treating lung adenocarcinoma. Graphical Abstract
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spelling doaj.art-4b29378cbfe34e9ea2d6de2784bdd3472023-07-16T11:20:22ZengSpringerDiscover Oncology2730-60112023-07-0114111910.1007/s12672-023-00748-6Veillonella parvula promotes the proliferation of lung adenocarcinoma through the nucleotide oligomerization domain 2/cellular communication network factor 4/nuclear factor kappa B pathwayWen Zeng0Yuhuan Wang1Zhe Wang2Mengge Yu3Kang Liu4Chengzhu Zhao5Yiyun Pan6Shudong Ma7Oncology Research Institute, Ganzhou Cancer Hospital, Gannan Medical UniversityDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityThe First Clinical College, Gannan Medical UniversityDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityOncology Research Institute, Ganzhou Cancer Hospital, Gannan Medical UniversityDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityAbstract Enrichment of Veillonella parvula in the lung microbiota is strongly associated with non-small cell lung cancer (NSCLC) and induces the progression of lung adenocarcinoma in vivo, but its actual role and mechanism remain unexplored. This study analyzed the correlation between NSCLC and V. parvula abundance based on 16 s rRNA sequencing results. The effects of V. parvula on the progression of lung adenocarcinoma were observed in vivo and in vitro using a C57 bl/6j mouse tumor-bearing model, a bacterial cell co-culture model, combined with transcriptome sequencing, and a TCGA database to explore and validate the growth promotion of lung adenocarcinoma by V. parvula and its molecular mechanism. 16 s rRNA sequencing revealed that V. parvula was significantly enriched in lung adenocarcinoma. In vivo, V. parvula promoted the growth of lung adenocarcinoma in mice by suppressing the infiltration of tumor-associated T lymphocytes and peripheral T lymphocytes. It showed a higher affinity for lung adenocarcinoma in vitro and promoted lung adenocarcinoma cell proliferation through adhesion or intracellular invasion. Further analysis of differential gene expression and KEGG enrichment by transcriptome sequencing revealed that V. parvula induced CCN4 expression and activated NOD-like receptor and NF-κB signaling pathway in lung adenocarcinoma cells. Further analysis clarified that V. parvula promoted activation of the NF-κB pathway via Nod2/CCN4 signaling, which promoted lung adenocarcinoma cell proliferation. Thus, V. parvula mediates activation of the Nod2/CCN4/NF-κB signaling pathway to promote non-small cell lung adenocarcinoma progression, thereby providing a potential target for diagnosing and treating lung adenocarcinoma. Graphical Abstracthttps://doi.org/10.1007/s12672-023-00748-6Veillonella parvulaLung adenocarcinoma16 s rRNA sequencingLLC cellsCCN4 expression
spellingShingle Wen Zeng
Yuhuan Wang
Zhe Wang
Mengge Yu
Kang Liu
Chengzhu Zhao
Yiyun Pan
Shudong Ma
Veillonella parvula promotes the proliferation of lung adenocarcinoma through the nucleotide oligomerization domain 2/cellular communication network factor 4/nuclear factor kappa B pathway
Discover Oncology
Veillonella parvula
Lung adenocarcinoma
16 s rRNA sequencing
LLC cells
CCN4 expression
title Veillonella parvula promotes the proliferation of lung adenocarcinoma through the nucleotide oligomerization domain 2/cellular communication network factor 4/nuclear factor kappa B pathway
title_full Veillonella parvula promotes the proliferation of lung adenocarcinoma through the nucleotide oligomerization domain 2/cellular communication network factor 4/nuclear factor kappa B pathway
title_fullStr Veillonella parvula promotes the proliferation of lung adenocarcinoma through the nucleotide oligomerization domain 2/cellular communication network factor 4/nuclear factor kappa B pathway
title_full_unstemmed Veillonella parvula promotes the proliferation of lung adenocarcinoma through the nucleotide oligomerization domain 2/cellular communication network factor 4/nuclear factor kappa B pathway
title_short Veillonella parvula promotes the proliferation of lung adenocarcinoma through the nucleotide oligomerization domain 2/cellular communication network factor 4/nuclear factor kappa B pathway
title_sort veillonella parvula promotes the proliferation of lung adenocarcinoma through the nucleotide oligomerization domain 2 cellular communication network factor 4 nuclear factor kappa b pathway
topic Veillonella parvula
Lung adenocarcinoma
16 s rRNA sequencing
LLC cells
CCN4 expression
url https://doi.org/10.1007/s12672-023-00748-6
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