20.500.12556/DiRROS-20010 Expression analysis of all protease genes reveals cathepsin K to be overexpressed in glioblastoma Background Cancer genome and transcriptome analyses advanced our understanding of cancer biology. We performed transcriptome analysis of all known genes of peptidases also called proteases and their endogenous inhibitors in glioblastoma multiforme (GBM), which is one of the most aggressive and deadly types of brain cancers, where unbalanced proteolysis is associated with tumor progression. Methods Comparisons were performed between the transcriptomics of primary GBM tumors and unmatched non-malignant brain tissue, and between GBM cell lines (U87-MG and U373) and a control human astrocyte cell line (NHA). Publicly-available data sets and our own datasets were integrated and normalized using bioinformatics tools to reveal protease and protease inhibitor genes with deregulated expression in both malignant versus non-malignant tissues and cells. Results Of the 311 protease genes identified to be differentially expressed in both GBM tissues and cells, 5 genes were highly overexpressed, 2 genes coding for non-peptidase homologues transferrin receptor (TFRC) and G protein-coupled receptor 56 (GPR56), as well as 3 genes coding for the proteases endoplasmic reticulum aminopeptidase 2 (ERAP2), glutamine-fructose-6-phosphate transaminase 2 (GFPT2) and cathepsin K (CTSK), whereas one gene, that of the serine protease carboxypeptidase E (CPE) was strongly reduced in expression. Seventy five protease inhibitor genes were differentially expressed, of which 3 genes were highly overexpressed, the genes coding for stefin B (CSTB), peptidase inhibitor 3 (PI3 also named elafin) and CD74. Seven out of 8 genes (except CSTB) were validated using RT-qPCR in GBM cell lines. CTSK overexpression was validated using RT-qPCR in GBM tissues as well. Cathepsin K immunohistochemical staining and western blotting showed that only proteolytically inactive proforms of cathepsin K were overexpressed in GBM tissues and cells. Conclusions The presence of high levels of inactive proforms of cathepsin K in GBM tissues and cells indicate that in GBM the proteolytic/collagenolytic role is not its primary function but it plays rather a different yet unknown role. glioblastoma multiforme genes true false true Angleški jezik Ni določen Neznano 2024-08-02 08:36:00 2024-08-02 08:36:00 2024-08-03 03:45:58 0000-00-00 00:00:00 2014 0 0 Nasl. z nasl. zaslona; Opis vira z dne 4. 11. 2014; Soavtorji: Helena Motaln, Ana Rotter, Nadia A. Atai, Kristina Gruden, Cornelis J. F. Van Noorden, Tamara T. Lah; str. 1- 12 iss. 10 Vol. 9 2014 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2014-10-30 616 1932-6203 10.1371/journal.pone.0111819 3237711 http://dx.doi.org/10.1371/journal.pone.0111819 1 b9d3c767-5088-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27828 RAZ_Verbovsek_Urska_2014.pdf RAZ_Verbovsek_Urska_2014.pdf 1 D28EC3AFE34AF51D6FBBCE1F5E5AD2F2 272305ef3af558ff157364e73f32a1e01aefcffe1261735afa250428d943d37e 37b637e3-5089-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27829 Nacionalni inštitut za biologijo 0 0 0