LOXL3 Silencing Affected Cell Adhesion and Invasion in U87MG Glioma Cells
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 sta...
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/15/8072 |
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| author | Talita de S. Laurentino Roseli da S. Soares Antonio M. Lerario Suely K. N. Marie Sueli M. Oba-Shinjo |
| author_facet | Talita de S. Laurentino Roseli da S. Soares Antonio M. Lerario Suely K. N. Marie Sueli M. Oba-Shinjo |
| author_sort | Talita de S. Laurentino |
| collection | DOAJ |
| description | 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 <i>LOXL3</i> expression levels. <i>LOXL3</i> 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 <i>LOXL3</i> 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. |
| first_indexed | 2024-03-10T09:15:20Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:15:20Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c4aa695b716c4940961f7a505191b1cf2023-11-22T05:42:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012215807210.3390/ijms22158072LOXL3 Silencing Affected Cell Adhesion and Invasion in U87MG Glioma CellsTalita de S. Laurentino0Roseli da S. Soares1Antonio M. Lerario2Suely K. N. Marie3Sueli M. Oba-Shinjo4Cellular and Molecular Biology Laboratory (LIM 15), Neurology Department, Faculdade de Medicina (FMUSP), Universidade de Sao Paulo, Sao Paulo 01246-000, SP, BrazilCellular and Molecular Biology Laboratory (LIM 15), Neurology Department, Faculdade de Medicina (FMUSP), Universidade de Sao Paulo, Sao Paulo 01246-000, SP, BrazilDepartment of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, USACellular and Molecular Biology Laboratory (LIM 15), Neurology Department, Faculdade de Medicina (FMUSP), Universidade de Sao Paulo, Sao Paulo 01246-000, SP, BrazilCellular and Molecular Biology Laboratory (LIM 15), Neurology Department, Faculdade de Medicina (FMUSP), Universidade de Sao Paulo, Sao Paulo 01246-000, SP, BrazilLysyl 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 <i>LOXL3</i> expression levels. <i>LOXL3</i> 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 <i>LOXL3</i> 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.https://www.mdpi.com/1422-0067/22/15/8072LOXL3lysyl oxidaseglioblastomacytoskeletonextracellular matrixcell death |
| spellingShingle | Talita de S. Laurentino Roseli da S. Soares Antonio M. Lerario Suely K. N. Marie Sueli M. Oba-Shinjo LOXL3 Silencing Affected Cell Adhesion and Invasion in U87MG Glioma Cells International Journal of Molecular Sciences LOXL3 lysyl oxidase glioblastoma cytoskeleton extracellular matrix cell death |
| title | LOXL3 Silencing Affected Cell Adhesion and Invasion in U87MG Glioma Cells |
| title_full | LOXL3 Silencing Affected Cell Adhesion and Invasion in U87MG Glioma Cells |
| title_fullStr | LOXL3 Silencing Affected Cell Adhesion and Invasion in U87MG Glioma Cells |
| title_full_unstemmed | LOXL3 Silencing Affected Cell Adhesion and Invasion in U87MG Glioma Cells |
| title_short | LOXL3 Silencing Affected Cell Adhesion and Invasion in U87MG Glioma Cells |
| title_sort | loxl3 silencing affected cell adhesion and invasion in u87mg glioma cells |
| topic | LOXL3 lysyl oxidase glioblastoma cytoskeleton extracellular matrix cell death |
| url | https://www.mdpi.com/1422-0067/22/15/8072 |
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