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P-MAPA and IL-12 Differentially Regulate Proteins Associated with Ovarian Cancer Progression: A Proteomic Study.

ABSTRACT: To investigate the potential role of immunotherapies in the cellular and molecular mechanisms associated with ovarian cancer (OC), we applied a comparative proteomic toll using protein identification combined with mass spectrometry. Herein, the effects of the protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride, known as P-MAPA, and the human recombinant interleukin-12 (hrIL-12) were tested alone or in combination in human SKOV-3 cells. The doses and period were defined based on a previous study, which showed that 25 ?g/mL P-MAPA and 1 ng/mL IL-12 are sufficient to reduce cell metabolism after 48 h. Indeed, among 2,881 proteins modulated by the treatments, 532 of them were strictly concordant and common. P-MAPA therapy upregulated proteins involved in tight junction, focal adhesion, ribosome constitution, GTP hydrolysis, semaphorin interactions, and expression of SLIT and ROBO, whereas it downregulated ERBB4 signaling, toll-like receptor signaling, regulation of NOTCH 4, and the ubiquitin proteasome pathway. In addition, IL-12 therapy led to upregulation of leukocyte migration, tight junction, and cell signaling, while cell communication, cell metabolism, and Wnt signaling were significantly downregulated in OC cells. A clear majority of proteins that were overexpressed by the combination of P-MAPA with IL-12 are involved in tight junction, focal adhesion, DNA methylation, metabolism of RNA, and ribosomal function; only a small number of downregulated proteins were involved in cell signaling, energy and mitochondrial processes, cell oxidation and senescence, and Wnt signaling. These findings suggest that P-MAPA and IL-12 efficiently regulated important proteins associated with OC progression; these altered proteins may represent potential targets for OC treatment in addition to its immunoadjuvant effects.

SUBMITTER: Junior LAL

PROVIDER: S-EPMC6933580 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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P-MAPA and IL-12 Differentially Regulate Proteins Associated with Ovarian Cancer Progression: A Proteomic Study.

Júnior Luiz Antonio Lupi LAL Cucielo Maira Smaniotto MS Domeniconi Raquel Fantin RF Dos Santos Lucilene Delazari LD Silveira Henrique Spaulonci HS da Silva Nunes Iseu I Martinez Marcelo M Martinez Francisco Eduardo FE Fávaro Wagner José WJ Chuffa Luiz Gustavo de Almeida LGA

ACS omega 20191211 26

To investigate the potential role of immunotherapies in the cellular and molecular mechanisms associated with ovarian cancer (OC), we applied a comparative proteomic toll using protein identification combined with mass spectrometry. Herein, the effects of the protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride, known as P-MAPA, and the human recombinant interleukin-12 (hrIL-12) were tested alone or in combination in human SKOV-3 cells. The doses and period were defined b ...[more]

PMID: 31891054

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Project description:BackgroundAbdominal aortic aneurysm (AAA) is a disease of high prevalence in old age, and its incidence gradually increases with increasing age. There were few studies about differences in the circulatory system in the incidence of AAA, mainly because younger patients with AAA are fewer and more comorbid nonatherosclerotic factors.MethodWe induced AAA in ApoE-/- male mice of different ages (10 or 24 weeks) and obtained plasma samples. After the top 14 most abundant proteins were detected, the plasma was analyzed by a proteomic study using the data-dependent acquisition (DDA) technique. The proteomic results were compared between different groups to identify age-related differentially expressed proteins (DEPs) in the circulation that contribute to AAA formation. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) network analyses were performed by R software. The top 10 proteins were determined with the MCC method of Cytoscape, and transcription factor (TF) prediction of the DEPs was performed with iRegulon (Cytoscape).ResultsThe aortic diameter fold increase was higher in the aged group than in the youth group (p < 0.01). Overall, 92 DEPs related to age and involved in AAA formation were identified. GO analysis of the DEPs showed enrichment of the terms wounding healing, response to oxidative stress, regulation of body fluid levels, ribose phosphate metabolic process, and blood coagulation. The KEGG pathway analysis showed enrichment of the terms platelet activation, complement and coagulation cascades, glycolysis/gluconeogenesis, carbon metabolism, biosynthesis of amino acids, and ECM-receptor interaction. The top 10 proteins were Tpi1, Eno1, Prdx1, Ppia, Prdx6, Vwf, Prdx2, Fga, Fgg, and Fgb, and the predicted TFs of these proteins were Nfe2, Srf, Epas1, Tbp, and Hoxc8.ConclusionThe identified proteins related to age and involved in AAA formation were associated with the response to oxidative stress, coagulation and platelet activation, and complement and inflammation pathways, and the TFs of these proteins might be potential targets for AAA treatments. Further experimental and biological studies are needed to elucidate the role of these age-associated and AAA-related proteins in the progression of AAA.

Project description:BackgroundTraumatic Heterotopic Ossification (tHO) is one of complications of elbow fractures to the detriment of patients' rehabilitation, and the severity of tHO corresponds to the size of ectopic bone. It has yet to be elucidated which proteins and pathways underlying the progression of tHO, and biomarkers to predict the severity of tHO at early stage of the disease also need further investigation.MethodsIn this study, a new rat model with distinct volume of ectopic bone was established first. Then a data-independent acquisition proteomics approach was used to investigate injured site tissues sequentially obtained from these rats (2, 7, 14, and 28 days post-injury). Differentially expressed analysis, functional annotation and co-expression analysis and protein-protein interaction network were performed to explore the pathways and hub proteins in the tHO progression. Clinical samples from a nest case-control study were used to validate the selected proteins for predicting the severity of tHO.ResultsThe Achilles Tenotomy (AT) induced significantly larger sizes of ectopic bone compared to Partial Achilles Tenotomy (PAT) in rat models. A total of 3547 quantifiable proteins were screened for differential expression analysis among the AT, PAT and control groups. The hierarchical clustering and expression pattern analysis revealed more apparent difference in the pathways such as oxidative phosphorylation, mitochondrial function, and sirtuin signaling between AT and PAT group at the early stage (2 dpi) of tHO. The co-expression analysis identified five hub proteins, UBA1, EIF3E, RPL17, RPL27, and RPS28. qPCR assay, immunoblot assay and immunohistochemistry assay verified that these proteins had higher expression level in the tissue samples of clinically relevant HO patients and clinically irrelevant HO patients than HO negative patients.ConclusionThe new established animal model and proteome profile could serve as a solid foundation for the comprehensive investigation of the progression of traumatic heterotopic ossification. And the identified 5 proteins (UBA1, EIF3E, RPL17, RPL27, and RPS28) may serve as potential biomarkers to predict the severity of tHO.The translational potential of this articleThe proteins identified in this study may be the potential biomarkers and therapeutic targets for predicting and treating the tHO at early stage.

Dataset Information

P-MAPA and IL-12 Differentially Regulate Proteins Associated with Ovarian Cancer Progression: A Proteomic Study.

Publications

P-MAPA and IL-12 Differentially Regulate Proteins Associated with Ovarian Cancer Progression: A Proteomic Study.

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