Netrin 4 (NTN4) is downregulated in breast cancer (BC) and can inhibit the migration of BC cells. miRNAs dysregulation plays prominent roles in BC tumorigenesis. However, the function of miR-17-5p, its relationship with NTN4 and its underlying functional mechanism in BC are unclear and were investigated in the current study. Compared with normal breast samples, miR-17-5p was upregulated in BC specimens in The Cancer Genome Atlas (TCGA). A clinical analysis based on TCGA showed that miR-17-5p expression correlated with BC tumor stage, lymph node status, estrogen receptor, and progesterone receptor status. A wound-healing assay and Transwell assay implied that miR-17-5p upregulation promotes BC cell migration and invasion. Reverse transcription-quantitative PCR and ELISA showed that NTN4 mRNA and protein were both downregulated after miR-17-5p was overexpressed in Hs578T cells, whereas miR-17-5p inhibition had the opposite effect in MCF-7 cells. We also performed a dual-fluorescent reporter assay, the results of which demonstrated that miR-17-5p represses NTN4 expression by directly targeting the 3' untranslated region of NTN4 mRNA. In summary, miR-17-5p considerably promotes BC cell migration by suppressing NTN4 expression, and may therefore offer a potential therapeutic target for BC.
Keywords: Breast cancer (BC); NTN4; miR-17-5p; migration.
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