J Cancer 2019; 10(19):4695-4706. doi:10.7150/jca.30596 This issue
1. Medicine Research Center, Weifang Medical University, Weifang, China.
2. Department of Oncology, Clinical Medical College, Weifang Medical University, Weifang, China
3. Department of Thyroid and Breast Surgery, Affiliated Hospital of Weifang Medical University, Weifang, China
4. Department of Pathology, Clinical Medical College, Weifang Medical University, Weifang, China.
5. College of Nursing, Weifang Medical University, Weifang, China.
6. College of Biological Science and Technology, Weifang Medical University, Weifang, China.
*Authors contributed equally
Epithelial-mesenchymal transition (EMT) is one of important steps that lead to cancer metastasis. Interleukin-22 (IL-22) is a T helper 17 (Th17) cells-secreted cytokine, it can promote invasion and metastasis of many cancers. MiR-486-5p is a microRNA that known to function as a tumor suppressor, and bioinformatics analysis predicts that Dock-1 has a binding site of miR-486-5p. In current research, we examined the relative expression levels of miR-486-5p and Dock-1 in 80 pairs of breast cancer tissues and corresponding adjacent normal tissues, also the effects of modifying their levels in cultured cells. We illustrated that IL-22 and Dock1 promote the invasion, metastasis, and EMT of breast cancer using Transwell invasion assay, western blot and immunofluorescence. MiR-486-5p directly bound the Dock1 mRNA 3' untranslated region and inhibited IL-22-induced EMT of breast cancer cells via the Dock1/NF-κB/Snail signaling pathway. Dock1 overexpression reversed the effect caused by the overexpression of miR-486-5p. Overexpression of miR-486-5p or downregulation of Dock1 reduced pulmonary metastasis in mice. This study provided insight into a potential mechanism where miRNAs regulate breast cancer metastasis and provided a novel therapeutic target for breast cancer treatment.
Keywords: miR-486-5p, epithelial-mesenchymal transition, Dock1, breast cancer, IL-22