Dataset Information

Prolactin and its receptor as therapeutic targets in glioblastoma multiforme.

ABSTRACT: Although prolactin (PRL) and its receptor (PRLR) have been detected in glioblastoma multiforme (GBM), their role in its pathogenesis remains unclear. Our aim was to explore their contribution in GBM pathogenesis. We detected PRL and PRLR in all GBM cell lines tested. PRLR activation or overexpression using plasmid transfection increased proliferation, viability, clonogenicity, chemoresistance and matrix metalloproteinase activity in GBM cells, while PRLR antagonist ?1-9-G129R-hPRL reduced their proliferation, viability, chemoresistance and migration. Meta-analysis of transcriptomic data indicated that PRLR was expressed in all grade II-III glioma (GII-III) and GBM samples. PRL was upregulated in GBM biopsies when compared to GII-III. While in the general population tumour PRL/PRLR expression did not correlate with patient survival, biological sex-stratified analyses revealed that male patients with PRL⁺/PRLR^HIGH GBM performed worse than PRL⁺/PRLR^LOW GBM. In contrast, all male PRL⁺/PRLR^HIGH GII-III patients were alive whereas only 30% of PRL⁺/PRLR^LOW GII-III patients survived after 100 months. Our study suggests that PRLR may be involved in GBM pathogenesis and could constitute a therapeutic target for its treatment. Our findings also support the notion that sexual dimorphism should be taken into account to improve the care of GBM patients.

SUBMITTER: Asad AS

PROVIDER: S-EPMC6925187 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Prolactin and its receptor as therapeutic targets in glioblastoma multiforme.

Asad Antonela Sofía AS Nicola Candia Alejandro Javier AJ Gonzalez Nazareno N Zuccato Camila Florencia CF Abt Araceli A Orrillo Santiago Jordi SJ Lastra Yael Y De Simone Emilio E Boutillon Florence F Goffin Vincent V Seilicovich Adriana A Pisera Daniel Alberto DA Ferraris María Jimena MJ Candolfi Marianela M

Scientific reports 20191220 1

Although prolactin (PRL) and its receptor (PRLR) have been detected in glioblastoma multiforme (GBM), their role in its pathogenesis remains unclear. Our aim was to explore their contribution in GBM pathogenesis. We detected PRL and PRLR in all GBM cell lines tested. PRLR activation or overexpression using plasmid transfection increased proliferation, viability, clonogenicity, chemoresistance and matrix metalloproteinase activity in GBM cells, while PRLR antagonist ∆1-9-G129R-hPRL reduced their ...[more]

PMID: 31862900

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Project description:MicroRNAs (miRNAs or miRs) contribute to the development of various malignant neoplasms, including glioblastoma multiforme (GBM). The present study aimed to explore the pathogenesis of GBM and to identify latent therapeutic agents for patients with GBM, based on an in silico analysis. Gene chips that provide miRNA expression profiling in GBM were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEMs) were also determined via the RobustRankAggreg algorithm. The target genes of DEMs were predicted and then intersected with GBM‑associated genes that were collected from the Gene Expression Profiling Interactive Analysis. Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the overlapping genes were then performed. Simultaneously, a connectivity map (CMap) analysis was performed to screen for potential therapeutic agents for GBM. A total of 10 DEMs (hsa‑miR‑196a, hsa‑miR‑10b, hsa‑miR‑196b, hsa‑miR‑18b, hsa‑miR‑542‑3p, hsa‑miR‑129‑3p, hsa‑miR‑1224‑5p, hsa‑miR‑876‑3p and hsa‑miR‑770‑5p) were obtained from three GEO gene chips (GSE25631, GSE42657 and GSE61710). Then, 1,720 target genes of the 10 miRNAs and 4,185 differently expressed genes in GBM were collected. By intersecting the aforementioned gene clusters, the present study identified 390 overlapping genes. GO and KEGG analyses of the 390 genes demonstrated that these genes were involved in certain cancer‑associated biological functions and pathways. Eight genes [(GTPase NRas (NRAS), calcium/calmodulin‑dependent protein kinase type II subunit Gamma (CAMK2G), platelet‑derived growth factor receptor alpha (PDGFRA), calmodulin 3 (CALM3), cyclin‑dependent kinase 6 (CDK6), calcium/calmodulin‑dependent protein kinase type II subunit beta (CAMK2B), retinoblastoma‑associated protein (RB1) and protein kinase C beta type (PRKCB)] that were centralized in the glioma pathway were selected for CMap analysis. Three chemicals (W‑13, gefitinib and exemestane) were identified as putative therapeutic agents for GBM. In summary, the present study identified three miRNA‑based chemicals for use as a therapy for GBM. However, more experimental data are needed to verify the therapeutic properties of these latent drugs in GBM.

Dataset Information

Prolactin and its receptor as therapeutic targets in glioblastoma multiforme.

Publications

Prolactin and its receptor as therapeutic targets in glioblastoma multiforme.

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