Downregulation of RCN1 inhibits esophageal squamous cell carcinoma progression and M2 macrophage polarization

Abstract

Abstract Background: Reticulocalbin 1 (RCN1) is a calcium-binding protein involved in the regulation of calcium homeostasis in the endoplasmic reticulum. The aim of this study was to explore the clinical value and biological role of RCN1 in esophageal squamous cell carcinoma (ESCC). In addition, we also investigated the effect of RCN1 on the polarization of tumor-associated macrophages (TAMs). Methods: The GSE53625 dataset from the Gene Expression Omnibus database was used to analyze the expression of RCN1 mRNA and the relationship with clinical value and immune cell infiltration. Immunohistochemistry was used to validate the expression of RCN1 and its correlation with clinicopathological characteristics. Subsequently, transwell and cell scratch assays were conducted to evaluate the migration and invasion abilities of ESCC cells. The expression levels of epithelial–mesenchymal transition (EMT)-related proteins were detected using Western blotting, while flow cytometry and Western blotting were employed to detect cell apoptosis. Additionally, qRT-PCR and Western blotting were utilized to evaluate the role of RCN1 in macrophage polarization. Results: RCN1is significantly upregulated in ESCC tissues and is closely associated with lymphatic metastasis and a poor prognosis; it is an independent prognostic factor for ESCC patients. Knockdown of RCN1 significantly inhibits migration, invasion, and EMT of ESCC cells, and promotes cell apoptosis. In addition, RCN1 downregulation inhibited the polarization of M2 macrophages. Conclusion: RCN1is upregulated in ESCC patients and is negatively correlated with patient prognosis. Knocking down RCN1 can inhibit the progression of ESCC cells and polarization of M2 macrophages. RCN1 could serve as a potential diagnostic and prognostic indicator for ESCC, and targeting RCN1 is a very promising therapeutic target.