LOXL3 Silencing Affected Cell Adhesion and Invasion in U87MG Glioma Cells.
Talita de Sousa LaurentinoRoseli da S SoaresAntonio M LerarioSuely Kazue Nagahashi MarieSueli Mieko Oba-ShinjoPublished in: International journal of molecular sciences (2021)
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 LOXL3 expression levels. LOXL3 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 LOXL3 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.
Keyphrases
- cell adhesion
- rna seq
- cell proliferation
- single cell
- cell death
- cell cycle arrest
- poor prognosis
- induced apoptosis
- extracellular matrix
- signaling pathway
- genome wide
- end stage renal disease
- pi k akt
- stem cells
- cell surface
- chronic kidney disease
- gene expression
- ejection fraction
- bone marrow
- cell cycle
- endoplasmic reticulum stress
- high throughput
- peritoneal dialysis
- dna methylation
- prognostic factors
- pseudomonas aeruginosa
- molecular docking
- molecular dynamics simulations
- binding protein