Liu Liu1, Yongjie Hu, Jingye Fu, Xihu Yang, Zhiyuan Zhang. 1. Department of Oral and Maxillofacial Surgery, School of Stomatology, The 9th People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. cycstal2004@hotmail.com
Abstract
BACKGROUND: The carcinogenesis mechanism of adenoid cystic carcinoma (ACC) of the salivary gland is poorly understood. MicroRNA155 (miRNA155) has been involved in the carcinogenesis of many malignant tumors. The present study aims to examine the role of miRNA155 in tumor growth and invasion of ACC. METHODS: MiRNA155 expression was determined in ACC specimens along with normal salivary glands by quantitative PCR. Using ACC-2 cells as a model for ACC, cell proliferation was examined by MTT assay after knocking down miRNA155 expression, and cell cycle analysis was performed. Invasive capacity of ACC-2 cells was examined by a Transwell culture assay. The effect of miRNA155 on tumor growth was also examined in vivo using mouse models. The effect of miRNA155 on epidermal growth factor receptor (EGFR)/NF-κB was studied by quantitative PCR and electrophoretic mobility shift assay. RESULTS: MiRNA155 was over-expressed in ACC. Proliferation of ACC-2 cells was markedly inhibited by knocking down miRNA155, resulting from a blockade of cell cycle in the G1 phase. Inhibition of miRNA155 significantly suppressed the invasive capacity of ACC-2 cells. In vivo growth of ACC-2 cell-derived tumors was significantly slower by inhibition of miRNA155. Inhibition of miRNA155 also resulted in decreased expression of EGFR and RelA (NF-κB). CONCLUSION: The results suggest that miRNA155 facilitates cell cycle progression and promotes invasion in ACC and that the EGFR/NF-κB pathway might participate in mediating the effects of miRNA155. This study has provided insights into the carcinogenic mechanisms of ACC and identified new targets for intervention of salivary ACC.
BACKGROUND: The carcinogenesis mechanism of adenoid cystic carcinoma (ACC) of the salivary gland is poorly understood. MicroRNA155 (miRNA155) has been involved in the carcinogenesis of many malignant tumors. The present study aims to examine the role of miRNA155 in tumor growth and invasion of ACC. METHODS:MiRNA155 expression was determined in ACC specimens along with normal salivary glands by quantitative PCR. Using ACC-2 cells as a model for ACC, cell proliferation was examined by MTT assay after knocking down miRNA155 expression, and cell cycle analysis was performed. Invasive capacity of ACC-2 cells was examined by a Transwell culture assay. The effect of miRNA155 on tumor growth was also examined in vivo using mouse models. The effect of miRNA155 on epidermal growth factor receptor (EGFR)/NF-κB was studied by quantitative PCR and electrophoretic mobility shift assay. RESULTS:MiRNA155 was over-expressed in ACC. Proliferation of ACC-2 cells was markedly inhibited by knocking down miRNA155, resulting from a blockade of cell cycle in the G1 phase. Inhibition of miRNA155 significantly suppressed the invasive capacity of ACC-2 cells. In vivo growth of ACC-2 cell-derived tumors was significantly slower by inhibition of miRNA155. Inhibition of miRNA155 also resulted in decreased expression of EGFR and RelA (NF-κB). CONCLUSION: The results suggest that miRNA155 facilitates cell cycle progression and promotes invasion in ACC and that the EGFR/NF-κB pathway might participate in mediating the effects of miRNA155. This study has provided insights into the carcinogenic mechanisms of ACC and identified new targets for intervention of salivary ACC.
Authors: Maria Denaro; Elena Navari; Clara Ugolini; Veronica Seccia; Valentina Donati; Augusto Pietro Casani; Fulvio Basolo Journal: PLoS One Date: 2019-01-25 Impact factor: 3.240