The targeted regulation of Gli1 by miR-361 to inhibit epithelia-mesenchymal transition and invasion of esophageal carcinoma cells.

Epithelia-mesenchymal transition (EMT) is critical for invasion and metastasis of esophageal carcinoma. Gli1, a transcriptional factor in Hedgehog pathway, is correlated with EMT, invasion and metastasis of tumors. However, its role in esophageal cancer is still unknown. Bioinformatics analysis revealed relationship between microRNA (miR)-361 and 3'-UTR of Gli1 gene. This study thus investigated the role of miR-361 and Gli1 in invasion and metastasis of esophageal cancer. Both tumor and adjacent tissues were collected from 58 esophageal cancer patients to test the expressions of miR-361 and Gli1, the relationship of which was confirmed by dual-luciferase reporter gene assay. Cultured esophageal cancer cells EC9706 were transfected with mimic NC, miR-361 mimic, si-NC, si-Gli1, miR-361 mimics+si-Glil, pQC or pQC-FU-Gli1. Transwell and colony formation assays were performed for cell invasion and attachment-independent growth. Expressions of Gli1, Snail, E-cadherin and N-cadherin proteins were revealed by Western blotting. The expression of Gli1 was significantly elevated in esophageal cancer tissues, along with lower miR-361 expression which was correlated with TNM stage. MiR-361 inhibited the expression of Gli1 via targeting on 3'-UTR of Gli1 gene. The transfection of miR-361 mimics and/or si-Gli1 significantly suppressed the growth of malignant cells. The over-expression of miR-361 and/or silencing of Gli1 decreased intracellular expression of Gli1, Snail and N-cadherin, and increased E-cadherin expression to suppress EMT and invasion of tumor cells while the opposite effects were obtained by over-expression of Gli1. Abnormal elevation of Gli1 and decrease of miR-361 were found in esophageal cancer tissues. MiR-361 weakened invasion of cancer cells and impeded EMT process via the inhibition of Gli1.