Usefulness of microRNA-375 as a prognostic and therapeutic tool in esophageal squamous cell carcinoma

Abstract

The aim of this study was to clarify the importance of microRNA-375 (miR-375) expression in patients with esophageal squamous cell carcinoma (ESCC) and to examine the in vivo antitumor effects of miR-375 in a model of ESCC using a non-viral delivery system. We estimated the miR-375 and LDHB and AEG-1/MTDH mRNA expression of the ESCC tumors from 85 patients. The correlation between the miR-375 expression and clinicopathological features, including the prognosis, were evaluated. The presence of high miR-375 expression was associated with lymphatic vessel invasion, while a low expression of miR-375 significantly correlated with a poor prognosis for the 85 ESCC patients. We also found that there was a significant inverse correlation between the expression of miR-375 and that of LDHB. Before the examination of miR-375 in the in vivo assay, we confirmed that atelocollagen prolonged the accumulation of miRNA by using fluorescently-labeled miRNA and an in vivo imaging system. We injected the miR-375/atelocollagen complex or a control-miRNA/atelocollagen complex into mice bearing TE2 and T.Tn xenografts via subcutaneous (s.c.) injections. The growth of both the TE2 and T.Tn tumors in the miR-375 groups was significantly suppressed compared with that in the control-miRNA groups. In addition, The LDHB mRNA expression of TE2 xenografts was significantly downregulated after miR-375 treatment. In conclusion, it might be possible for the level of miR-375 expression to be a utilized as a prognostic indicator for ESCC patients. The administration of miR-375 using a non-viral delivery might represent a powerful new treatment for ESCC.