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  1. Article ; Online: Correlation of the tumor escape phenotype with loss of PRELP expression in melanoma

    Helene Schäfer / Karthikeyan Subbarayan / Chiara Massa / Christoforos Vaxevanis / Anja Mueller / Barbara Seliger

    Journal of Translational Medicine, Vol 21, Iss 1, Pp 1-

    2023  Volume 16

    Abstract: Abstract Background Despite immunotherapies having revolutionized the treatment of advanced cutaneous melanoma, effective and durable responses were only reported in a few patients. A better understanding of the interaction of melanoma cells with the ... ...

    Abstract Abstract Background Despite immunotherapies having revolutionized the treatment of advanced cutaneous melanoma, effective and durable responses were only reported in a few patients. A better understanding of the interaction of melanoma cells with the microenvironment, including extracellular matrix (ECM) components, might provide novel therapeutic options. Although the ECM has been linked to several hallmarks of cancer, little information is available regarding the expression and function of the ECM protein purine-arginine-rich and leucine-rich protein (PRELP) in cancer, including melanoma. Methods The structural integrity, expression and function of PRELP, its correlation with the expression of immune modulatory molecules, immune cell infiltration and clinical parameters were determined using standard methods and/or bioinformatics. Results Bioinformatics analysis revealed a heterogeneous, but statistically significant reduced PRELP expression in available datasets of skin cutaneous melanoma when compared to adjacent normal tissues, which was associated with reduced patients’ survival, low expression levels of components of the MHC class I antigen processing machinery (APM) and interferon (IFN)-γ signal transduction pathway, but increased expression of the transforming growth factor (TGF)-β isoform 1 (TFGB1) and TGF-β receptor 1 (TGFBR1). In addition, a high frequency of intra-tumoral T cells directly correlated with the expression of MHC class I and PRELP as well as the T cell attractant CCL5 in melanoma lesions. Marginal to low PRELP expression levels were found in the 47/49 human melanoma cell lines analysis. Transfection of PRELP into melanoma cell lines restored MHC class I surface expression due to transcriptional upregulation of major MHC class I APM and IFN-γ pathway components. In addition, PRELP overexpression is accompanied by high CCL5 secretion levels in cell supernatant, an impaired TGF-β signaling as well as a reduced cell proliferation, migration and invasion of melanoma cells. Conclusions Our ...
    Keywords PRELP ; Melanoma ; MHC class I ; Antigen processing ; Immunogenicity ; IFN signaling ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2023-09-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Expression, Regulation and Function of microRNA as Important Players in the Transition of MDS to Secondary AML and Their Cross Talk to RNA-Binding Proteins

    Marcus Bauer / Christoforos Vaxevanis / Nadine Heimer / Haifa Kathrin Al-Ali / Nadja Jaekel / Michael Bachmann / Claudia Wickenhauser / Barbara Seliger

    International Journal of Molecular Sciences, Vol 21, Iss 7140, p

    2020  Volume 7140

    Abstract: Myelodysplastic syndromes (MDS), heterogeneous diseases of hematopoietic stem cells, exhibit a significant risk of progression to secondary acute myeloid leukemia (sAML) that are typically accompanied by MDS-related changes and therefore significantly ... ...

    Abstract Myelodysplastic syndromes (MDS), heterogeneous diseases of hematopoietic stem cells, exhibit a significant risk of progression to secondary acute myeloid leukemia (sAML) that are typically accompanied by MDS-related changes and therefore significantly differ to de novo acute myeloid leukemia (AML). Within these disorders, the spectrum of cytogenetic alterations and oncogenic mutations, the extent of a predisposing defective osteohematopoietic niche, and the irregularity of the tumor microenvironment is highly diverse. However, the exact underlying pathophysiological mechanisms resulting in hematopoietic failure in patients with MDS and sAML remain elusive. There is recent evidence that the post-transcriptional control of gene expression mediated by microRNAs (miRNAs), long noncoding RNAs, and/or RNA-binding proteins (RBPs) are key components in the pathogenic events of both diseases. In addition, an interplay between RBPs and miRNAs has been postulated in MDS and sAML. Although a plethora of miRNAs is aberrantly expressed in MDS and sAML, their expression pattern significantly depends on the cell type and on the molecular make-up of the sample, including chromosomal alterations and single nucleotide polymorphisms, which also reflects their role in disease progression and prediction. Decreased expression levels of miRNAs or RBPs preventing the maturation or inhibiting translation of genes involved in pathogenesis of both diseases were found. Therefore, this review will summarize the current knowledge regarding the heterogeneity of expression, function, and clinical relevance of miRNAs, its link to molecular abnormalities in MDS and sAML with specific focus on the interplay with RBPs, and the current treatment options. This information might improve the use of miRNAs and/or RBPs as prognostic markers and therapeutic targets for both malignancies.
    Keywords myelodysplastic syndrome ; secondary acute myeloid leukemia ; microRNA ; RNA-binding protein ; therapy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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