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

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 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 RCN1mRNA and itsrelationship 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 evaluated by Western blot, while apoptosis was detected by flow cytometry and Western blot. Additionally, qRT‒PCR was utilized to evaluate the role of RCN1 in macrophage polarization. Results: RCN1 was significantly upregulated in ESCC tissues and was closely associated with lymphatic metastasis and a poor prognosis, and was an independent prognostic factor for ESCC in patients. Knockdown of RCN1significantly inhibited the migration, invasion, and EMT of ESCC cells, and promoted cell apoptosis. In addition, RCN1 downregulation inhibited inhibited M2 polarization. Conclusion: RCN1 is upregulated in ESCC patients and is negatively correlated with patient prognosis. Knocking down RCN1 inhibits ESCC progression and M2 polarization. RCN1 can serve as a potential diagnostic and prognostic indicator for ESCC, and targeting RCN1 is a very promising therapeutic strategy.