Open Access

Integrative genomic analyses of a novel cytokine, interleukin-34 and its potential role in cancer prediction

  • Authors:
    • Bo Wang
    • Wenming Xu
    • Miaolian Tan
    • Yan Xiao
    • Haiwei Yang
    • Tian-Song Xia
  • View Affiliations

  • Published online on: November 12, 2014     https://doi.org/10.3892/ijmm.2014.2001
  • Pages: 92-102
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Interleukin-34 (IL-34) is a novel cytokine, which is composed of 222 amino acids and forms homodimers. It binds to the macrophage colony-stimulating factor (M-CSF) receptor and plays an important role in innate immunity and inflammatory processes. In the present study, we identified the completed IL-34 gene in 25 various mammalian genomes and found that IL-34 existed in all types of vertebrates, including fish, amphibians, birds and mammals. These species have a similar 7 exon/6 intron gene organization. The phylogenetic tree indicated that the IL-34 gene from the primate lineage, rodent lineage and teleost lineage form a species-specific cluster. It was found mammalian that IL-34 was under positive selection pressure with the identified positively selected site, 196Val. Fifty-five functionally relevant single nucleotide polymorphisms (SNPs), including 32 SNPs causing missense mutations, 3 exonic splicing enhancer SNPs and 20 SNPs causing nonsense mutations were identified from 2,141 available SNPs in the human IL-34 gene. IL-34 was expressed in various types of cancer, including blood, brain, breast, colorectal, eye, head and neck, lung, ovarian and skin cancer. A total of 5 out of 40 tests (1 blood cancer, 1 brain cancer, 1 colorectal cancer and 2 lung cancer) revealed an association between IL-34 gene expression and cancer prognosis. It was found that the association between the expression of IL-34 and cancer prognosis varied in different types of cancer, even in the same types of cancer from different databases. This suggests that the function of IL-34 in these tumors may be multidimensional. The upstream transcription factor 1 (USF1), regulatory factor X-1 (RFX1), the Sp1 transcription factor 1 , POU class 3 homeobox 2 (POU3F2) and forkhead box L1 (FOXL1) regulatory transcription factor binding sites were identified in the IL-34 gene upstream (promoter) region, which may be involved in the effects of IL-34 in tumors.
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January-2015
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Copy and paste a formatted citation
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Spandidos Publications style
Wang B, Xu W, Tan M, Xiao Y, Yang H and Xia T: Integrative genomic analyses of a novel cytokine, interleukin-34 and its potential role in cancer prediction. Int J Mol Med 35: 92-102, 2015
APA
Wang, B., Xu, W., Tan, M., Xiao, Y., Yang, H., & Xia, T. (2015). Integrative genomic analyses of a novel cytokine, interleukin-34 and its potential role in cancer prediction. International Journal of Molecular Medicine, 35, 92-102. https://doi.org/10.3892/ijmm.2014.2001
MLA
Wang, B., Xu, W., Tan, M., Xiao, Y., Yang, H., Xia, T."Integrative genomic analyses of a novel cytokine, interleukin-34 and its potential role in cancer prediction". International Journal of Molecular Medicine 35.1 (2015): 92-102.
Chicago
Wang, B., Xu, W., Tan, M., Xiao, Y., Yang, H., Xia, T."Integrative genomic analyses of a novel cytokine, interleukin-34 and its potential role in cancer prediction". International Journal of Molecular Medicine 35, no. 1 (2015): 92-102. https://doi.org/10.3892/ijmm.2014.2001