Parvimonas micra Infection Enhances Proliferation, Wound Healing, and Inflammation of a Colorectal Cancer Cell Line.
Bioscience reports(2023)
摘要
The gut microbiota Parvimonas micra has been found to be enriched in gut mucosal tissues and fecal samples of colorectal cancer (CRC) patients compared to non-CRC controls. In this study, we investigated the tumorigenic potential of P. micra and its regulatory pathways in CRC using HT-29, a low-grade CRC intestinal epithelial cell. For every P. micra-HT-29 interaction assay, HT-29 was co-cultured anaerobically with P. micra at an MOI of 100:1 (bacteria: cells) for 2 hr. We found that P. micra increased HT-29 cell proliferation by 38.45% (P=0.008), with the highest wound healing rate at 24 hr post-infection (P=0.02). In addition, inflammatory marker expression (IL-5, IL-8, CCL20, CSF2) was also significantlyinduced. Shotgun proteomics profiling analysis revealed that P. micra affects the protein expression of HT-29 (157 up-regulated; 214 down-regulated proteins). Upregulation of PSMB4 protein and its neighbouring subunits revealed association of the ubiquitin-proteasome pathway in CRC carcinogenesis; whereas downregulation of CUL1, YWHAH, and MCM3 signified cell cycle dysregulation. Moreover, 22 clinically relevant epithelial-mesenchymal transition (EMT)-markers were expressed in HT-29 infected with P. micra. Overall, this study elucidated exacerbated oncogenic properties of P. micra in HT-29 via aberrant cell proliferation, enhanced wound healing, inflammation, upregulation of ubiquitin-proteasome pathway (UPPs) and activation of EMT pathways.
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关键词
colorectal cancer cell line,infection,wound healing,inflammation
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