Liposome Nanoparticles Carrying miR-22 Suppress Proliferation, Invasion and Epithelial–Mesenchymal Transition (EMT) of Laryngeal Squamous Cell Carcinoma by Targeting Wingless-Related Integration Site (WNT) Pathway

Abstract

Abnormal miR-22 level is related to laryngeal squamous cell carcinoma (LSCC) progression. This study mainly assessed its role in proliferation, invasion and EMT of LSCC and their possible mechanisms of action. HN4 was collected, and corresponding groups were set as; blank group, positive control group, miR-22 group and MIRNA-22 NC group. Pathway inhibitor group and pathway agonist group were also set. The expressions of miR-22, EMT-related genes, cell proliferation rate, invasion rate, β-catenin and Cyclin D1 were observed. Results revealed that, expressions of miR-22 and e-cadherin were higher in the blank group and miR-22 NC group, while N-cadherin and Vimentin levels were lower. Moreover, miR-22 and EMT-related genes in the positive control group and miR-22 group were opposite (P <0.05). The proliferation rate and invasion rate of blank and miR-22 NC groups were also lower, while positive control and miR-22 groups showed different changes (P <0.05). β-catenin and Cyclin D1 expressions in the blank group and miR-22 NC group were increased compared to other two groups. The proliferation rate, invasion rate, expression of N-cadherin and Vimentin were higher and E-cadherin was lower in blank and pathway agonist group, which was opposite in the pathway inhibitor group (P < 0.05). β-catenin and Cyclin D1 protein levels in blank and pathway agonist groups were higher than pathway inhibitor group (P < 0.05). A binding region between miR-22 gene sequence and 3′UTR 215-229 sequence of Wnt gene was found and Wnt was found to be the target gene for miR-22. The fluorescence intensity of mutant plasmid was higher than wild-type plasmid (P <0.05). miR-22 can inhibit LSCC proliferation, invasion and EMT and the main mechanism of action is related to the Wnt signaling pathway. MiR-22 targeted Wnt gene and inhibited Wnt signaling pathway activity, lower key factor beta catenin expression Wnt pathways, thereby inhibiting factor laryngeal squamous cancer cells proliferation, Cyclin D1 expression, resulting in inhibition of cell proliferation, and EMT process at the same time, reducing the cell invasion ability, inhibiting the growth of laryngeal squamous cancer cells. Eventually, the Wnt pathways or miR-22 all can be used as targets for laryngeal squamous carcinoma.