Cellular and Molecular Biology Laboratory (LIM 15), Neurology Department, Faculdade de Medicina (FMUSP), Universidade de Sao Paulo, Sao Paulo 01246-000, SP, Brazil.
Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA.
Int J Mol Sci. 2021 Jul 28;22(15):8072. doi: 10.3390/ijms22158072.
Lysyl oxidase-like 3 (LOXL3), belonging to the lysyl oxidase family, is responsible for the crosslinking in collagen or elastin. The cellular localization of LOXL3 is in the extracellular space by reason of its canonical function. In tumors, the presence of LOXL3 has been associated with genomic stability, cell proliferation, and metastasis. In silico analysis has shown that glioblastoma was among tumors with the highest expression levels. silencing of U87MG cells by siRNA led to the spreading of the tumor cell surface, and the transcriptome analysis of these cells revealed an upregulation of genes coding for extracellular matrix, cell adhesion, and cytoskeleton components, convergent to an increase in cell adhesion and a decrease in cell invasion observed in functional assays. Significant correlations of expression with genes coding for tubulins were observed in the mesenchymal subtype in the TCGA RNA-seq dataset of glioblastoma (GBM). Conversely, genes involved in endocytosis and lysosome formation, along with MAPK-binding proteins related to focal adhesion turnover, were downregulated, which may corroborate the observed decrease in cell viability and increase in the rate of cell death. Invasiveness is a major determinant of the recurrence and poor outcome of GBM patients, and downregulation of LOXL3 may contribute to halting the tumor cell invasion.
赖氨酰氧化酶样蛋白 3（LOXL3）属于赖氨酰氧化酶家族，负责胶原蛋白或弹性蛋白的交联。由于其典型功能，LOXL3 的细胞定位在细胞外空间。在肿瘤中，LOXL3 的存在与基因组稳定性、细胞增殖和转移有关。计算机分析表明，胶质母细胞瘤是表达水平最高的肿瘤之一。通过 siRNA 沉默 U87MG 细胞导致肿瘤细胞表面扩散，这些细胞的转录组分析显示编码细胞外基质、细胞黏附和细胞骨架成分的基因上调，与功能测定中观察到的细胞黏附增加和侵袭减少一致。在胶质母细胞瘤 TCGA RNA-seq 数据集的间充质亚型中，观察到 LOXL3 的表达与编码微管蛋白的基因呈显著相关性。相反，参与内吞作用和溶酶体形成的基因以及与粘着斑周转相关的 MAPK 结合蛋白下调，这可能证实观察到的细胞活力下降和细胞死亡速度增加。侵袭性是胶质母细胞瘤患者复发和预后不良的主要决定因素，LOXL3 的下调可能有助于阻止肿瘤细胞的侵袭。
