MicroRNA-375 suppresses esophageal cancer cell growth and invasion by repressing metadherin expression

Abstract

Accumulating evidence indicates that aberrant expression of microRNAs is involved in tumorigenesis, tumor progression and response to therapy. MicroRNA-375 (miR-375) is an important cancer-associated RNA that is downregulated in multiple types of cancer. In the present study, the potential effects of and underlying molecular mechanism for miR-375 in esophageal cancer were investigated. The expression of miR-375 in paired esophageal squamous cell carcinoma (ESCC) and non-tumor tissues from 10 patients was quantified using the reverse transcription-quantitative polymerase chain reaction. The miR-375 levels in the ESCC cell line EC109 and a normal esophageal epithelial cell line, Het-1A, were also detected. The effect of miR-375 on ESCC cell growth and invasion was determined using Cell Counting kit-8, flow cytometry and invasion assays. A luciferase assay was conducted for target identification. The results of the present study revealed that miR-375 was downregulated in ESCC tumor tissue and EC109 cells compared with normal tissue and Het-1A cells (P<0.01). Overexpression of miR-375 inhibited EC109 cell growth and invasion, and induced cell cycle arrest. In addition, metadherin (MTDH) was demonstrated to be a direct target of miR-375 (P<0.01). The overexpression of miR-375 downregulated MTDH (P<0.01), cyclin D1 (P<0.05) and vascular endothelial growth factor (P<0.01) expression, while upregulating epithelial cadherin (P<0.01) expression, which may account for its effect on ESCC cell proliferation and invasion. The results of the present study suggest that the miR-375/MTDH axis represents a target for the treatment of ESCC.