Wei-Wei Wang1, Bin Chen2, Cheng-Bin Lei1, Guo-Xin Liu1, Ye-Gang Wang1, Chen Yi3, You-Yuan Wang3, Shan-Yi Zhang3. 1. Zibo Center Hospital, Zi Bo, China. 2. Department of Stomatology, The Affiliated Xuzhou Center Hospital of Nanjing University of Chinese Medicine, Xu zhou, China. 3. Guangdong Provincial Key Laboratory of Malignant Tumor, Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Abstract
OBJECTIVE: Neurotropism of salivary adenoid cystic carcinoma (SACC) and pulmonary metastasis may lead to in treatment failure. miR-582-5p plays important roles in tumorigenesis, invasion and migration. Here, we aim to determine the effect of miR-582-5p and its role in SACC invasion and metastasis. METHODS: Six primary human SACC samples and matching adjacent normal tissues were analyzed by microarray analysis. Next, quantitative real-time PCR was carried out to evaluate miR-582-5p expression in 16 primary human SACC samples and matching adjacent normal tissues. Cell invasion and migration were also analyzed, and a luciferase reporter assay and western analysis were conducted. Cell growth and apoptosis assay were performed to confirm the effect of miR-582-5p and Forkhead box C1 (FOXC1) siRNA in cell proliferation and apoptosis. SACC tumorigenesis and metastasis were investigated in vivo experiment. Clinical samples from 110 patients were analyzed using in situ hybridization and immunohistochemistry. RESULTS: Microarray analysis revealed that miR-582-5p was significantly downregulated in the SACC samples compared with the matching adjacent normal tissues. Regulation of miR-582-5p expression significantly influenced the migration, invasion and proliferation ability of SACC cells by targeting FOXC1. E-cadherin was increased, while vimentin and snail were decreased with downregulation of FOXC1, suggesting that FOXC1 may regulate the epithelial-to-mesenchymal transition (EMT) of SACC cells by transactivating snail. In vivo, miR-582-5p overexpression suppressed the tumorigenesis and pulmonary metastasis of SACC. Lower expression of miR-582-5p expression predicts unfavorable prognoses and high rates of metastasis. CONCLUSIONS: miR-582-5p could suppress effect on the process of invasion and migration in SACC cell lines, and this could occur through its target gene FOXC1.
OBJECTIVE: Neurotropism of salivary adenoid cystic carcinoma (SACC) and pulmonary metastasis may lead to in treatment failure. miR-582-5p plays important roles in tumorigenesis, invasion and migration. Here, we aim to determine the effect of miR-582-5p and its role in SACC invasion and metastasis. METHODS: Six primary human SACC samples and matching adjacent normal tissues were analyzed by microarray analysis. Next, quantitative real-time PCR was carried out to evaluate miR-582-5p expression in 16 primary human SACC samples and matching adjacent normal tissues. Cell invasion and migration were also analyzed, and a luciferase reporter assay and western analysis were conducted. Cell growth and apoptosis assay were performed to confirm the effect of miR-582-5p and Forkhead box C1 (FOXC1) siRNA in cell proliferation and apoptosis. SACC tumorigenesis and metastasis were investigated in vivo experiment. Clinical samples from 110 patients were analyzed using in situ hybridization and immunohistochemistry. RESULTS: Microarray analysis revealed that miR-582-5p was significantly downregulated in the SACC samples compared with the matching adjacent normal tissues. Regulation of miR-582-5p expression significantly influenced the migration, invasion and proliferation ability of SACC cells by targeting FOXC1. E-cadherin was increased, while vimentin and snail were decreased with downregulation of FOXC1, suggesting that FOXC1 may regulate the epithelial-to-mesenchymal transition (EMT) of SACC cells by transactivating snail. In vivo, miR-582-5p overexpression suppressed the tumorigenesis and pulmonary metastasis of SACC. Lower expression of miR-582-5p expression predicts unfavorable prognoses and high rates of metastasis. CONCLUSIONS: miR-582-5p could suppress effect on the process of invasion and migration in SACC cell lines, and this could occur through its target gene FOXC1.