TRIM22 confers poor prognosis and promotes epithelial-mesenchymal transition through regulation of AKT/GSK3β/β-catenin signaling in non-small cell lung cancer

// Li Liu 1 , Xiao-Ming Zhou 2 , Fang-Fei Yang 1 , Yuan Miao 3 , Yan Yin 1 , Xue-Jun Hu 1 , Gang Hou 1 , Qiu-Yue Wang 1 and Jian Kang 1 1 Department of Respiratory Medicine, The First Hospital of China Medical University, Shenyang 110001, China 2 Department of Respiratory Medicine, The Shengjing Hospital of China Medical University, Shenyang 110004, China 3 Department of Pathology, The First Hospital and College of Basic Medical Sciences, China Medical University, Shenyang 110001, China Correspondence to: Gang Hou, email: hougangcmu@163.com Keywords: TRIM22, prognosis, non-small cell lung cancer, proliferation, invasion Received: November 30, 2016 Accepted: May 23, 2017 Published: July 01, 2017 ABSTRACT 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.