Tumor microenvironment-related gene selenium-binding protein 1 (SELENBP1) is associated with immunotherapy efficacy and survival in colorectal cancer.

BACKGROUND: Selenium-binding protein 1 (SELENBP1), a member of the selenium-containing protein family, plays an important role in malignant tumorigenesis and progression. However, it is currently lacking research about relationship between SELENBP1 and immunotherapy in colorectal cancer (CRC). METHODS: We first analyzed the expression levels of SELENBP1 based on the Cancer Genome Atlas (TCGA), Oncomine andUALCAN. Chisq.test, Fisher.test, Wilcoxon-Mann-Whitney test and logistic regression were used to analyze the relationship of clinical characteristics with SELENBP1 expression. Then Gene ontology/ Kyoto encyclopedia of genes and genomes (GO/KEGG), Gene set enrichment analysis (GSEA) enrichment analysis to clarify bio-processes and signaling pathways. The cBioPortal was used to perform analysis of mutation sites, types, etc. of SELENBP1. In addition, the correlation of SELENBP1 gene with tumor immune infiltration and prognosis was analyzed using ssGSEA, ESTIMATE, tumor immune dysfunction and rejection (TIDE) algorithm and Kaplan-Meier (KM) Plotter database. Quantitative real-time PCR (qRT-PCR) and western blotting (WB) were used to validate the expression of SELENBP1 in CRC samples and matched normal tissues. Immunohistochemistry (IHC) was further performed to detect the expression of SELENBP1 in CRC samples and matched normal tissues. RESULTS: We found that SELENBP1 expression was lower in CRC compared to normal colorectal tissue and was associated with poor prognosis. The aggressiveness of CRC increased with decreased SELENBP1 expression. Enrichment analysis showed that the SELENBP1 gene was significantly enriched in several pathways, such as programmed death 1 (PD-1) signaling, signaling by interleukins, TCR signaling, collagen degradation, costimulation by the CD28 family. Decreased expression of SELENBP1 was associated with DNA methylation and mutation. Immune infiltration analysis identified that SELENBP1 expression was closely related to various immune cells and immune chemokines/receptors. With increasing SELENBP1 expression, immune and stromal components in the tumor microenvironment were significantly decreased. SELENBP1 expression in CRC patients affects patient prognosis by influencing tumor immune infiltration. Beside this, SELENBP1 expression is closely related to the sensitivity of chemotherapy and immunotherapy. CONCLUSIONS: Survival analysis as well as enrichment and immunoassay results suggest that SELENBP1 can be considered as a promising prognostic biomarker for CRC. SELENBP1 expression is closely associated with immune infiltration and immunotherapy. Collectively, our study provided useful information on the oncogenic role of SELENBP1, contributing to further exploring the underlying mechanisms.

Berberine Attenuates Cell Motility via Inhibiting Inflammation-Mediated Lysyl Hydroxylase-2 and Glycolysis.

Lysyl hydroxylase-2 (LH2) involves in the hydroxylation of telopeptide lysine residues during collagen deposition. Recent studies indicate that interleukin (IL)-6 generated by the chronic inflammation disease may trigger the LH2 expression to accelerate cell motility. Berberine is the alkaloid derived from the traditional Chinese medicine Coptis chinensis, which displays potential anti-inflammatory activity in multiple diseases. The anti-inflammatory activity of berberine has been confirmed by reducing proinflammatory cytokines such as IL-6, IL-8, and IFN-γ. However, whether and how berberine inhibits cellular motility against metastatic spread in triple-negative breast cancer (TNBC) has not been demonstrated, and the underlying mechanism remains unclear. We investigated the effects of berberine on the inflammatory cytokine secretion, cell proliferation, and migration in vitro and further explored the effect of berberine on growth and metastasis in vivo. Berberine restrained TNBC cell proliferation, motility, and glycolysis process in a dose-dependent way. The secretion of IL-6 was abrogated by berberine in TNBC cells, and IL-6-stimulated cell migration was inhibited by berberine. Mechanistically, berberine remarkably suppressed LH2 expression at both mRNA and protein levels. LH2 depletion led to decreasing the antimotility effect of berberine, and this phenomenon was related to the suppressed glycolysis after LH2 inhibition. Conversely, ectopic restoration of LH2 could further increase the antimotility effect of berberine. Moreover, berberine was confirmed to inhibit cell growth and motility in vivo, and the expression of LH2 and glycolytic enzymes was also blocked by berberine in vivo. Collectively, this study indicated that berberine could be a promising therapeutic drug via regulating LH2 for TNBC.