Oncotarget

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This article has been corrected. Correction in: Oncotarget. 2021; 12:1442-1443.

Procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 promotes hypoxia-induced glioma migration and invasion

Yangyang Xu, Lin Zhang, Yuzhen Wei, Xin Zhang, Ran Xu, Mingzhi Han, Bing Huang, Anjing Chen, Wenjie Li, Qing Zhang, Gang Li, Jian Wang, Peng Zhao and Xingang Li _

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Oncotarget. 2017; 8:23401-23413. https://doi.org/10.18632/oncotarget.15581

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Abstract

Yangyang Xu1, Lin Zhang2, Yuzhen Wei1,3, Xin Zhang1, Ran Xu1, Mingzhi Han1, Bing Huang1, Anjing Chen1, Wenjie Li1, Qing Zhang1, Gang Li1, Jian Wang1,4, Peng Zhao1, Xingang Li1

1Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan 250012, China

2Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan 250012, China

3Department of Neurosurgery, Jining No.1 People’s Hospital, Jining 272011, China

4Department of Biomedicine, University of Bergen, 5009 Bergen, Norway

Correspondence to:

Xingang Li, email: lixg@sdu.edu.cn

Peng Zhao, email: drzhaopeng@163.com

Keywords: hypoxia, procollagen-lysine 2-oxoglutarate 5-dioxygenase 2, FAK, glioma, invasion

Received: December 22, 2016     Accepted: February 13, 2017     Published: February 21, 2017

ABSTRACT

Poor prognosis of glioblastoma multiforme is strongly associated with the ability of tumor cells to invade the brain parenchyma, which is believed to be the major factor responsible for glioblastoma recurrence. Therefore, identifying the molecular mechanisms driving invasion may lead to the development of improved therapies for glioblastoma patients. Here, we investigated the role of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2), an enzyme catalyzing collagen cross-linking, in the biology of glioblastoma invasion. PLOD2 mRNA was significantly overexpressed in glioblastoma compared to low-grade tumors based on the Oncomine datasets and REMBRANDT database for human gliomas. Kaplan-Meier estimates based on the TCGA dataset demonstrated that high PLOD2 expression was associated with poor prognosis. In vitro, hypoxia upregulated PLOD2 protein in U87 and U251 human glioma cell lines. siRNA knockdown of endogenous HIF-1α or treatment of cells with the HIF-1α inhibitor PX-478 largely abolished the hypoxia-mediated PLOD2 upregulation. Knockdown of PLOD2 in glioma cell lines led to decreases in migration and invasion under normoxia and hypoxia. In addition, levels of phosphorylated FAK (Tyr 397), an important kinase mediating cell adhesion, were reduced in U87-shPLOD2 and U251-shPLOD2 cells, particularly under hypoxic conditions. Finally, orthotopic U251-shPLOD2 xenografts were circumscribed rather than locally invasive. In conclusion, the results indicated that PLOD2 was a gene of clinical relevance with implications in glioblastoma invasion and treatment strategies.


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