Hypoxia-induced PLOD2 promotes proliferation, migration and invasion via PI3K/Akt signaling in glioma
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Ye Song1,*, Shihao Zheng1,*, Jizhou Wang1,*, Hao Long1, Luxiong Fang1, Gang Wang1, Zhiyong Li1, Tianshi Que1, Yi Liu1, Yilei Li2, Xi’an Zhang1, Weiyi Fang3 and Songtao Qi1
1Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, PR China
2Department of Pharmacology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, PR China
3Cancer Center, TCM-Integrated Hospital, Southern Medical University Guangzhou, Guangdong, 510515, PR China
*These authors contributed equally to this work
Xi’an Zhang, email: email@example.com
Weiyi Fang, email: firstname.lastname@example.org
Songtao Qi, email: email@example.com
Keywords: PLOD2, glioma, epithelial–mesenchymal transition, PI3K/AKT, hypoxia
Received: April 29, 2016 Accepted: March 08, 2017 Published: March 30, 2017
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.
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