MicroRNA-223 Suppresses the Progression of Esophageal Cancer by Negatively Regulating SMAD Family Member 4

Abstract

The purpose of this study was to elucidate the biological role of MicroRNA-223 (miRNA-223) in mediating the malignant progression of esophageal cancer and the underlying mechanism. MiRNA-223 levels were measured using qRT-PCR in 50 paired esophageal cancer tissues and adjacent paracancerous tissues. The correlation between miRNA-223 level and pathological indicators in esophageal cancer patients was analyzed. In vitro experiments assessed the impact of miRNA-223 on the proliferative, migratory, and invasive abilities of esophageal cancer cells. Additionally, rescue experiments were conducted to investigate the involvement of miRNA-223 and its downstream target, SMAD4, in the progression of esophageal cancer. Esophageal cancer tissues showed decreased levels of miRNA-223 compared to adjacent tissues. Patients with low miRNA-223 exhibited higher rates of lymphatic and distant metastasis, as well as poorer overall survival than those with high miRNA-223 levels. Increasing miRNA-223 in TE-1 and EC-109 cells reduced their proliferative, migratory, and invasive capabilities. Esophageal cancer tissues and cell lines displayed elevated SMAD4 levels, which were negatively regulated by miRNA-223. Restoring SMAD4 expression partially reversed the inhibitory effects of miRNA-223 overexpression in esophageal cancer cells. MiRNA-223 is closely correlated to lymphatic metastasis, distant metastasis and poor prognosis of esophageal cancer patients. MiRNA-223 suppresses proliferative, migratory and invasive abilities of esophageal cancer cells via negatively regulating SMAD4.