MiRNA-375 regulates the cell survival and apoptosis of human non-small cell carcinoma by targeting HER2

Abstract

micro (mi)-RNAs are a class of small non-coding RNAs that regulate gene expression by binding to the 3'-untranslated region of mRNA, which may lead to mRNA degradation or transcription regulation. Previous studies indicated that miRNAs are important for the pathogenesis of human cancer. MIR-375 has been implicated in various tumor types; however, the biological activity in human non-small cell lung carcinoma (NSCLC) cells remains to be fully elucidated. The purpose of the present study was to investigate the biological importance of MIR-375 in human NSCLC cells. The expression of miRNAs and mRNA was determined using reverse transcription-quantitative polymerase chain reaction. Cell proliferation was analyzed using a Cell Counting kit-8 assay. Cell apoptosis was analyzed using a fluorescence-activated cell sorting assay. The migration and invasion abilities of cells were evaluated using an in vivo mouse model. Dual-luciferase assay and western blotting were used to determine the potential target of MIR-375. The results indicated that the expression of MIR-375 in human NSCLC cells was significantly downregulated and induction of MIR-375 may inhibit the proliferation of human NSCLC cells by inducing apoptosis. An animal model was used to determine that the upregulation of MIR-375 inhibited the migration and invasion of A549 human NSCLC cells in vivo. It was also determined that human epidermal growth factor receptor 2 (HER-2) was a direct target gene of MIR-375 and induction of MIR-375 may reduce the expression of HER-2 in human NSCLC cells. These findings suggested that MIR-375 may act as a potential therapeutic target for human NSCLC cancer in the future.