TRIM22 confers poor prognosis and promotes epithelial-mesenchymal transition through regulation of AKT/GSK3β/β-catenin signaling in non-small cell lung cancer
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Li Liu1, Xiao-Ming Zhou2, Fang-Fei Yang1, Yuan Miao3, Yan Yin1, Xue-Jun Hu1, Gang Hou1, Qiu-Yue Wang1 and Jian Kang1
1Department of Respiratory Medicine, The First Hospital of China Medical University, Shenyang 110001, China
2Department of Respiratory Medicine, The Shengjing Hospital of China Medical University, Shenyang 110004, China
3Department of Pathology, The First Hospital and College of Basic Medical Sciences, China Medical University, Shenyang 110001, China
Gang Hou, email: firstname.lastname@example.org
Keywords: TRIM22, prognosis, non-small cell lung cancer, proliferation, invasion
Received: November 30, 2016 Accepted: May 23, 2017 Published: July 01, 2017
Expression pattern and biological roles of TRIM22 remains unknown in most human cancers. The present study aims to discover its clinical significance and function in human non-small cell lung cancer (NSCLC). Immunohistochemistry was used to examine TRIM22 expression in 126 cases of NSCLC specimens. TRIM22 protein was upregulated in 70/126 (55.6%) non-small cell lung cancer tissues compared with normal lung tissue. TRIM22 overexpression was associated with advanced TNM stage, positive nodal metastasis and poor prognosis. Plasmid and siRNA transfection were performed in lung cancer cell lines. TRIM22 overexpression promoted proliferation, colony formation and invasion in A549 cells. While its depletion exhibited the opposite effects in H1299 cell line. TRIM22 overexpression promoted cell cycle progression through regulation of cyclin D1, cyclin E and p27. TRIM22 also changed the expression of epithelial to mesenchymal transition (EMT) markers including E-cadherin N-cadherin, Vimentin and Snail. Furthermore, TRIM22 activated PI3K/AKT/GSK3β/β-catenin oncogenic signaling pathways. Treatment with PI3K inhibitor LY294002 and β-catenin siRNA blocked the effects of TRIM22 on EMT in TRIM22-overexpressing cells. In conclusion,TRIM22 serves as an important oncoprotein and a promoter of cell proliferation and invasion through AKT/ GSK3β/β-catenin induced EMT in NSCLC.
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