Downregulation of microRNA-3646 Through Direct Targeting of F-Box Protein 4 on Interleukin-17-Induced Lung Cancer Cell Migration and Invasion

Abstract

IL-17 participates in the initiation and growth of malignant cancers, including lung cancer. The aberrant expression of miRNA is also related to tumor growth and metastasis. Studies have confirmed that high expression of miRNA-3646 can boost breast cancer cell invasion and migration, suggesting that miRNA-3646 is a tumor-promoting factor. However, the role of miRNA-3646 in the migration and invasion of IL-17-induced lung cancer cells is unclear. In this study, qRT-PCR was used to determine the level of miRNA-3646. We found that in lung cancer cells, miRNA-3646 levels exceeded those of normal bronchial epithelial 16HBE cells (P < 0.05). The level of miRNA-3646 in NCI-H1299 cells was higher than that in A549, NCI-H446, and SK-MES-1 cells (P < 0.05). After IL-17 treatment, the number of proliferating and migrating lung carcinoma NCI-H1299 cells increased, transport of vimentin increased, and transport of E-cadherin decreased (P < 0.05). After IL-17 treatment, the number of proliferating and migrating lung carcinoma NCI-H1299 cells transfected with miRNA-3646 inhibitor decreased, transport of vimentin decreased, and transport of E-cadherin increased (P < 0.05). FBXO4 siRNA reversed the inhibition of miRNA-3646 on the proliferation and migration of IL-17-induced lung carcinoma NCI-H1299 cells and the transport of E-cadherin and vimentin. Thus, downregulation of miRNA-3646 inhibited IL-17-induced lung carcinoma cell migration and proliferation by directly targeting FBXO4.