AUTHOR=Shen Jiyu , Ni Yalan , Guan Qijie , Li Rui , Cao Hong , Geng Yan , You Qingjun 

TITLE=Stenotrophomonas maltophilia promotes lung adenocarcinoma progression by upregulating histone deacetylase 5

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1121863

DOI=10.3389/fmicb.2023.1121863

ISSN=1664-302X

ABSTRACT=Lung cancer is the leading cause of cancer death worldwide, and the lung adenocarcinoma (LADC) is the most common lung cancer. Lung cancer has a distinct microbiome composition correlated with patients’ smoking status. However, the causal evidence of microbial impacts on LADC is largely unknown. Here, we investigated microbial communities’ differences in Formalin-Fixed Paraffin-Embedded tissues of ever-smoke (n=22) and never-smoke (n=31) patients with LADC through bacterial 16S rRNA gene high-throughput sequencing. Although alpha and beta diversity were comparable, we found a significant increase of genus Stenotrophomonas in LADC tissues of patient with primary tumor size greater than 3cm and never-smoker patients. We further found that intratracheal infection with Stenotrophomonas maltophilia (S. maltophilia) promoted tumor progression in nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung cancer mouse model. We performed RNA-seq analysis on lung tissues and found that S. maltophilia treatment drove inflammation and upregulated tumor associated cell signaling, including Apelin signaling pathway. Mechanistically, Histone Deacetylase 5 (HDAC5) gene expression was significantly upregulated in S. maltophilia treated groups, and was required for S. maltophilia induced cell proliferation and migration in LADC cell line A549. Therefore, we provide in vivo and in vitro evidence to demonstrate that S. maltophilia promotes LADC progression, in part, through HDAC5.