MicroRNA-124-3p directly targets PDCD6 to inhibit metastasis in breast cancer

Breast cancer (BC) is the leading cause of cancer-associated mortality among women worldwide, with a poor 5-year survival rate, particularly among patients with metastatic BC. Previous studies have indicated that the dysregulation of microRNAs (miRNAs/miRs) is associated with carcinogenesis and metastasis. Thus, investigating the underlying molecular mechanisms by which miRNAs mediate their effects may aid in the improvement of BC treatment. In the present study, reverse transcription-quantitative polymerase chain reaction analyses were performed to investigate miR-124-3p expression in BC tissues. The expression of miR-124-3p was significantly decreased in primary BC tissues compared with that in adjacent non-tumor tissues. Downregulated miR-124-3p was correlated with lymph node metastasis and a low overall survival time. Wound-healing and Transwell assays revealed that MDA-MB-231 and MCF-7 cell motility was inhibited by miR-124-3p, but was promoted by a miR-124-3p inhibitor. Overexpression of miR-124-3p increased levels of E-cadherin, and decreased levels of N-cadherin and Vimentin, indicating that miR-124-3p inhibits the epithelial-mesenchymal transition. In addition, a bioinformatics analysis and subsequent in vitro experiments identified programmed cell death protein 6 (PDCD6) as a direct target of miR-124-3p. Restoration of PDCD6 expression impaired the metastasis inhibitor role of miR-124-3p by promoting cell invasion. Furthermore, the expression of miR-124-3p was inversely associated with PDCD6 mRNA levels in clinical breast tumors. Taken together, these data suggest that miR-124-3p inhibits tumor metastasis by inhibiting PDCD6 expression, and that the miR-124-3p/PDCD6 signaling axis may be a potential target for novel treatments in patients with advanced BC.