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.
Highlights
Gliomas are the most common form of malignant primary brain tumors in adults, with an annual incidence of approximately four to five per 100,000 people [1]
To determine whether PLOD2 plays a role in glioma tumorigenesis, quantitative real time PCR was initially conducted to determine the expression of PLOD2 mRNA transcripts in 50 frozen glioma tissues and 30 normal brain tissues
Altered PLOD2 expression was observed in glioblastoma [13], the biological functions of PLOD2 in glioma tumorigenesis and progression have not been well characterized
Summary
Gliomas are the most common form of malignant primary brain tumors in adults, with an annual incidence of approximately four to five per 100,000 people [1]. Despite of the therapeutic advances that had been made in the past few decades, such as surgical resection, adjuvant radiotherapy and chemotherapy, the overall 5-year survival rate of glioma patients still remains poor [2, 3]. Majority of glioma patients succumb to this disease within 2 years of diagnosis [4]. A great challenge lies ahead in understanding the molecular mechanisms of glioma tumorigenesis to identify novel prognostic molecular markers as well as to develop novel therapeutic strategies. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2(PLOD2), known as LH2, TLH2 or BRKS2, is a membrane-bound homodimeric enzyme that hydroxylates lysines in the telopeptide of procollagens [5]. PLOD2 expression has been found to provide prognostic information about bladder cancer, hepatocellular carcinoma and glioblastoma [13,14,15]. PLOD2 was detected to be involved in agiogenesis after ischemic stroke, related to reconstruction of basal lumina, this correlation implies that PLOD2 might be a potential target in anti-angiogenesis treatment [16]
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