CgB promotes EMT and stemness via MAPK pathway in colonic neuroendocrine carcinoma.

The incidence of colorectal neuroendocrine tumors is increasing every year with poor prognosis. Members of Chromogranin family proteins have been shown to be associated with cancer metastasis; however, the role of chromogranin B in colonic neuroendocrine carcinoma (NEC) is unknown. In this study, we investigated the expression and function of CgB in colonic NEC. Using RNA-seq data from GSE 9576 and GSE 142720 datasets, we analyzed the differentially expressed genes between the normal and NEC samples, which protein levels were further validated using the Human Protein Atlas (HPA) databases. Moreover, immunohistochemistry staining and biological experiments were conducted to examine the expression and function of CgB in colonic NEC. Western blot was also performed to confirm the effect of CgB on epithelial mesenchymal transition (EMT) and its related pathways. We found that the expression level of CgB was significantly higher in colonic NEC tissues than in the adjacent tissues. The upregulation of CgB promoted cell invasion and migration as well as activated EMT and stemness. Mechanistically, both pathway enrichment analysis and Western blot analysis confirmed that CgB overexpression activated p38 MAPK and ERK pathways, while silencing CgB showed the opposite effects. Collectively, our results suggested that CgB activated p38 MAPK and ERK pathways, thereby contributing to the development of colonic NEC.