MicroRNA-375 inhibits esophageal squamous cell carcinoma proliferation through direct targeting of SP1.

Abstract

Several studies have shown that microRNA-375 (miR-375) is frequently downregulated in several types of human cancer including gastric cancer, colorectal cancer and oral squamous cell carcinoma. However, the role of miR-375 in human esophageal cancer remains unknown. In the current study, the expression level of miR-375 was analyzed in 43 esophageal squamous cell carcinoma (ESCC) tissue and matched adjacent normal tissue samples from patients with ESCC by reverse transcription-quantitative polymerase chain reaction. In addition, the expression level of miR-375 was analyzed in ESCC cell lines (KYSE450 and KYSE150) and the human esophageal epithelial cell line Het-1A by the same method. The expression level of miR-375 was significantly downregulated in ESCC tissue samples and cell lines compared with adjacent normal tissue samples and the human esophageal epithelial cell line, respectively. The effect of miR-375 on ESCC cell proliferation was detected by cell counting kit-8 (CCK-8) and colony formation assays. miR-375 overexpression significantly decreased ESCC cell proliferation and colony formation. Bioinformatics analysis was used to predict specificity protein 1 (SP1) as a target gene of miR-375 in ESCC, and this was verified by dual-luciferase assay. The present study demonstrated that SP1 regulates ESCC cell proliferation and colony formation through direct interaction with miR-375. In addition, the overall survival of patients with ESCC was analyzed using the Kaplan-Meier method and log-rank test. The results indicated that patients with ESCC with high miR-375 expression had a better survival rate compared with patients with ESCC with low miR-375 expression. Taken together, these results suggest that downregulated miR-375 promotes ESCC cell proliferation and colony formation via direct targeting of SP1, and this association may contribute to ESCC progression.