Parvimonas micra activates the Ras/ERK/c-Fos pathway by upregulating miR-218-5p to promote colorectal cancer progression

Abstract

Background Colorectal cancer (CRC) is the third most common cancer in the world, and a strong relationship exists between CRC and gut microbiota, which affects the occurrence, development, and metastasis of cancer. Bioinformatics-based analyses revealed that the abundance of Parvimonas micra (P. micra) in the feces of patients with cancer is significantly higher than that in healthy people. Therefore, an important relationship may exist between P. micra and CRC. Methods We first confirmed that P. micra can promote the proliferation of cell lines through cell experiments and mouse models. Then we selected the signaling pathways and content of exosomes to promote the development of CRC by transcriptomics and microRNA sequencing. Finally, we confirmed that P. micra promoted CRC development through miR-218-5p/Ras/ERK/c-Fos pathway through the in vivo and in vitro experiments. Results First, it was confirmed by in vitro and in vivo experiments that P. micra can promote the development of CRC. Transcriptome analysis after the coincubation of bacteria and cells revealed that P. micra promoted cell proliferation by activating the Ras/ERK/c-Fos pathway. Furthermore, microRNA sequencing analysis of the cells and exosomes showed that miR-218-5p and protein tyrosine phosphatase receptor R (PTPRR) were the key factors involved in activating the Ras/ERK/c-Fos pathway, and the miR-218-5p inhibitor was used to confirm the role of microRNA in xenograft mice. Conclusion This experiment confirmed that P. micra promoted the development of CRC by upregulating miR-218-5p expression in cells and exosomes, inhibiting PTPRR expression, and ultimately activating the Ras/ERK/c-Fos signaling pathway.

StableMate: a statistical method to select stable predictors in omics data

“…Of note, two species, Dialister pneumosintes and Parvimonas micra , were selected by Lasso and RF but not by StableMate (Figure 5B). In particular, Parvimonas micra is known to be associated with CRC as it promotes tumourigenesis (Chang et al, 2023; Zhao et al, 2022). However, StableMate identified these two species as predictive but not significantly stable.…”

Characterization of Lung and Oral Microbiomes in Lung Cancer Patients Using Culturomics and 16S rRNA Gene Sequencing

“… P. micra is highly abundant in patients with colorectal cancer and promotes colorectal tumorigenesis by inducing colonocyte proliferation and altering the Th17 immune response ( 31 , 32 ). Our previous results showed that P. micra promoted colorectal cancer progression by upregulating miR-218-5p expression and ultimately activating the Ras/ERK/c-Fos signaling pathway ( 33 ). However, its correlation with lung cancer has not yet been reported.…”

Parvimonas micra can translocate from the subgingival sulcus of the human oral cavity to colorectal adenocarcinoma

“…[ 16 ] proved that P. micra causes hypermethylations in the promoters of genes related to the cytoskeleton, such as SCIN and DIAPH3 , in tumor suppressor genes, such as TSPAN13 , HACE1 , SEMA3F and SASH1 , and in epithelial‐mesenchymal transition genes such FBXO32 , in colon cells. A recent study also demonstrated that these periodontal bacteria can also promote CRC development increasing the expression of a specific microRNA (miR‐218‐5p) in cells and exosomes, inhibiting the expression of PTPRR and enhancing the RAS/ERK/C‐FOS signaling pathway, which leads to colon cells overgrowth [ 105 ]. It is important to note that Zhao et al.…”