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Gene set enrichment analysis of the NF-κB/Snail/YY1/RKIP circuitry in multiple myeloma

  • Research Article
  • Published:
Tumor Biology

Abstract

The presence of a dysregulated NF-κB/Snail/YY1/RKIP loop was recently established in metastatic prostate cancer cells and non-Hodgkin’s lymphoma; however, its involvement in multiple myeloma (MM) has yet to be investigated. Aim of the study was to investigate the role of the NF-κB/Snail/YY1/RKIP circuitry in MM and how each gene is correlated with the remaining genes of the loop. Using gene set enrichment analysis and gene neighbours analysis in data received from four datasets included in the Multiple Myeloma Genomics Portal of the Multiple Myeloma Research Consortium, we identified various enriched gene sets associated with each member of the NF-κB/Snail/YY1/RKIP circuitry. In each dataset, the 20 most co-expressed genes with the circuitry genes were isolated subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment. Among many, we highlighted on FNDC3B, TPD52, BBX, MBNL1 and MFAP2. Many co-expressed genes participated in the regulation of metabolic processes and nucleic acid binding, or were transcription factor binding genes and genes with metallopeptidase activity. The transcription factors FOXO4, GATA binding factor, Sp1 and AP4 most likely affect the expression of the NF-κB/Snail/YY1/RKIP circuitry genes. Computational analysis of various GEO datasets revealed elevated YY1 and RKIP levels in MM vs. the normal plasma cells, as well as elevated RKIP levels in MM vs. normal B lymphocytes. The present study highlights the relationships of the NF-κB/Snail/YY1/RKIP circuitry genes with specific cancer-related gene sets in multiple myeloma.

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Abbreviations

AML:

Acute myeloid leukemia

BBX:

Bobby sox homolog (Drosophila)

DLBCL:

Diffuse large B-cell lymphoma

EMT:

Epithelial-to-mesenchymal transition

ES:

Enrichment score

FNDC3B:

Fibronectin type III domain containing 3B

GEO:

Gene expression omnibus

GO:

Gene ontology

GSEA:

Gene set enrichment analysis

KEGG:

Kyoto encyclopedia of genes and genomes

MBNL1:

Muscleblind-like splicing regulator 1

MFAP2:

Microfibrillar-associated protein 2

MGUS:

Monoclonal gammopathy of undetermined significance

MM:

Multiple myeloma

NES:

Normalised enrichment score

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NHL:

Non-Hodgkin’s lymphoma

PTEN:

Phosphatase and tensin homologue

RKIP:

Raf-1 kinase inhibitor protein

Snail:

Snail family zinc finger 1

TFBMs:

Transcription factor binding motifs

TPD52:

Tumour protein D52

YY1:

Yin Yang 1

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Authors and Affiliations

  1. Laboratory of Virology, Medical School, University of Crete, 71110, Heraklion, Greece

    Apostolos Zaravinos & Demetrios A. Spandidos

  2. Molecular Medicine Research Center (MMRC), Department of Biological Sciences, University of Cyprus, 1678, Nicosia, Cyprus

    Apostolos Zaravinos

  3. Department of Hematology, University Hospital of Heraklion, Crete, Greece

    Peggy Kanellou

  4. 1st Department of Pediatrics, Choremeio Research Laboratory, University of Athens, 11527, Athens, Greece

    George Ι. Lambrou

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  1. Apostolos Zaravinos
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  2. Peggy Kanellou
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  3. George Ι. Lambrou
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  4. Demetrios A. Spandidos
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Correspondence to Apostolos Zaravinos.

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Zaravinos, A., Kanellou, P., Lambrou, G.Ι. et al. Gene set enrichment analysis of the NF-κB/Snail/YY1/RKIP circuitry in multiple myeloma. Tumor Biol. 35, 4987–5005 (2014). https://doi.org/10.1007/s13277-014-1659-9

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  • DOI: https://doi.org/10.1007/s13277-014-1659-9

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