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Expression data from WIF1 induced LN-229 (GBM cell line)

ABSTRACT: Glioblastoma is the most aggressive primary brain tumor in adults and due to the invasive nature it cannot be completely removed. We have recently shown that the WNT inhibitory factor 1 (WIF1), a secreted inhibitor of WNTs, is downregulated in glioblastoma and acts as strong tumor suppressor. In search of a mediator for this function differential gene expression profiles of WIF1-expressing cells were performed. MALAT1, a long non-coding RNA and key positive regulator of invasion, emerged as the top downregulated gene. Indeed, knock-down of MALAT1 reduced migration in glioblastoma cells, without effect on proliferation. LN-229 cells induced with Doxocyclin to express WIF1 were compared to the non-induced control (two biological replicates each)

ORGANISM(S): Homo sapiens

SUBMITTER: Vassallo Irene

PROVIDER: S-ECPF-GEOD-58525 | biostudies-other |

REPOSITORIES: biostudies-other

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Project description:BackgroundGonadotropin-releasing hormone (GnRH) receptor, a rhodopsin-like G-protein coupled receptor (GPCR) family member involved in GnRH signaling, is reported to be expressed in several tumors including glioblastoma multiforme (GBM), one of the most malignant and aggressive forms of primary brain tumors. However, the molecular targets associated with GnRH receptor are not well studied in GBM or in other cancers. The present study aims at investigating the effect of GnRH agonist (Gosarelin acetate) on cell proliferation and associated signaling pathways in GBM cell line, LN229.MethodsLN229 cells were treated with different concentrations of GnRH agonist (10-10 M to 10-5 M) and the effect on cell proliferation was analyzed by cell count method. Further, total protein was extracted from control and GnRH agonist treated cells (with maximum reduction in cell proliferation) followed by trypsin digestion, labeling with iTRAQ reagents and LC-MS/MS analysis to identify differentially expressed proteins. Bioinformatic analysis was performed for annotation of proteins for the associated molecular function, altered pathways and network analysis using STRING database.ResultsThe treatment with different concentrations of GnRH agonist showed a reduction in cell proliferation with a maximum reduction of 48.2% observed at 10-6 M. Quantitative proteomic analysis after GnRH agonist treatment (10-6 M) led to the identification of a total of 29 differentially expressed proteins with 1.3-fold change (23 upregulated, such as, kininogen-1 (KNG1), alpha-2-HS-glycoprotein (AHSG), alpha-fetoprotein (AFP), and 6 downregulated, such as integrator complex subunit 11 (CPSF3L), protein FRG1 (FRG1). Some of them are known [KNG1, AHSG, AFP] while others such as inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2), ITIH4, and LIM domain-containing protein 1 (LIMD1) are novel to GnRH signaling pathway. Protein-protein interaction analysis showed a direct interaction of KNG1, a hub molecule, with GnRH, GnRH receptor, EGFR and other interactors including ITIH2, ITIH4 and AHSG. Overexpression of KNG1 after GnRH agonist treatment was validated using Western blot analysis, while a significant inhibition of EGFR was observed after GnRH agonist treatment.ConclusionsThe study suggests a possible link of GnRH signaling with EGFR signaling pathways likely via KNG1. KNG1 inhibitors may be investigated independently or in combination with GnRH agonist for therapeutic applications.

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Expression data from WIF1 induced LN-229 (GBM cell line)

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