PRJNA545850
Gut butyrate-producing organisms correlate to Placenta Specific 8 protein in colon cells: importance to colorectal cancer progression
Patients with curative resection of colorectal cancer (CRC) frequently develop tumour relapse or distant metastasis. It has been reported that increased Placenta Specific 8 (PLAC8) expression in the stool may correlate with CRC recurrence. Insights into the role of PLAC8 in CRC relapse and its clinical significance may help in identifying strategies for preventing CRC recurrence and deterioration. PLAC8 was assessed in clinical tissues. Cell and animal models were used to clarify the roles of PLAC8 in CRC tumourigenesis, invasion, and migration. The gut microbiota was evaluated using next-generation sequencing to globally screen for 16S ribosomal DNA in stool and variations in the type of microbiota correlated with PLAC8 expression. We found that PLAC8 was upregulated in tissues from patients with late-stage CRC. In our in vitro studies, PLAC8 was dynamically regulated in mitotic cells. Overexpressed PLAC8 was nucleated at the centrosome during mitosis, and therefore, PLAC8 overexpression might increase cell growth and migration (all P < 0.05). The tumourigenic and invasive effects of PLAC8 on CRC cells were also confirmed in a xenograft mouse model. We identified reduced levels of two butyrate-producing organisms, Butyricicoccus and Prevotella spp., in stools from CRC patients. We found that butyrate downregulated PLAC8 expression and induced apoptosis in PLAC8-overexpressing cells. Our data suggests that PLAC8 gene and protein expression and dysbiosis of gut microflora, especially in butyrate-producing microorganisms, may be indicators of CRC progression.