Hypoxia-induced PLOD2 promotes proliferation, migration and invasion via PI3K/Akt signaling in glioma

// Ye Song 1, * , Shihao Zheng 1, * , Jizhou Wang 1, * , Hao Long 1 , Luxiong Fang 1 , Gang Wang 1 , Zhiyong Li 1 , Tianshi Que 1 , Yi Liu 1 , Yilei Li 2 , Xi’an Zhang 1 , Weiyi Fang 3 and Songtao Qi 1 1 Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, PR China 2 Department of Pharmacology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, PR China 3 Cancer Center, TCM-Integrated Hospital, Southern Medical University Guangzhou, Guangdong, 510515, PR China * These authors contributed equally to this work Correspondence to: Xi’an Zhang, email: zxa@smu.edu.cn Weiyi Fang, email: fangweiyi1975@163.com Songtao Qi, email: qisongtaosjwk@163.com Keywords: PLOD2, glioma, epithelial–mesenchymal transition, PI3K/AKT, hypoxia Received: April 29, 2016 Accepted: March 08, 2017 Published: March 30, 2017 ABSTRACT Gliomas are the most common form of malignant primary brain tumors with poor 5-year survival rate. Dysregulation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was observed in gliomas, but the specific role and molecular mechanism of PLOD2 in glioma have not been reported yet. In this study, PLOD2 was found to be frequently up-regulated in glioma and could serve as an independent prognostic marker to identify patients with poor clinical outcome. Knockdown of PLOD2 inhibited proliferation, migration and invasion of glioma cells in vitro and in vivo . Mechanistically, inhibition of PLOD2 inactivated PI3K/AKT signaling pathway and thus regulated the expression of its downstream epithelial–mesenchymal transition (EMT)-associated regulators, including E-cadherin, vimentin, N-cadherin, β-catenin, snail and slug in glioma cells. Moreover, PLOD2 could be induced by hypoxia-inducible factor-1α (HIF-1α) via hypoxia, thereby promoting hypoxia-induced EMT in glioma cells. Our data suggests that PLOD2 may be a potential therapeutic target for patients with glioma.