Clinical relevance of lysyl oxidase-like 2 and functional mechanisms in glioma

Abstract

Introduction: Glioma is the most frequent malignancy of the adult central nervous system with high recurrence risk and poor prognosis. Understanding the biological molecular mechanisms involved in glioma progression is critical for studying oncogenic mechanisms and improving prognosis. Lysyl oxidase-like 2 (LOXL2) is a kind of lysyl oxidase catalyzing the formation of peptidyl-lysine residues and promoting intramolecular cross-linking, especially for proteins in extracellular matrix. Our study explored the expression pattern of LOXL2 in glioma for the first time and found that its high expression was associated with larger tumor size and advanced tumor grade ( P <0.05). Moreover, univariate and multivariate analyses revealed LOXL2 as a novel independent prognostic factor for the overall survival of glioma patients. Methods: To evaluate the detailed functional roles of LOXL2, we tested its oncobiology characteristics in U87-MG cells with overexpression and knockdown experiments. Results: Cellular results demonstrated that LOXL2 overexpression enhanced cell proliferation and invasion, while LOXL2-siRNA attenuated cell viability. Furthermore, our data identified the participation of E-cadherin, Snail1, Src, and FAK proteins downstream of LOXL2. Notably, by using immunoprecipitation and mass spectrometry strategies, we initially verified the interaction between LOXL2 and HDAC2, indicating the existence of a protein complex containing LOXL2/Snail1/HDAC2. Additionally, the expression of HDAC2 protein was highly correlated with that of LOXL2 in clinical glioma tissues ( P =0.02), further implying the synergic oncogenic roles of these 2 proteins. Conclusion: LOXL2 is a promising prognostic biomarker and may be further evaluated as a potential drug target for patients with glioma. Keywords: glioma, HDAC2, invasion, LOXL2, prognosis