Integrative genomic analyses of a novel cytokine, interleukin-34 and its potential role in cancer prediction.
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.
Department of Medical Oncology, The Eastern Hospital of The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510700, P.R. China.
Bo
B
Wang
Department of Endocrinology, The Eastern Hospital of The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510700, P.R. China.
Wenming
W
Xu
Department of Medical Oncology, The Eastern Hospital of The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510700, P.R. China.
Miaolian
M
Tan
Department of Medical Oncology, The Eastern Hospital of The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510700, P.R. China.
Yan
Y
Xiao
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
Haiwei
H
Yang
Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
Tian-Song
TS
Xia
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D016207:Cytokines / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D030541:Databases, Genetic; D005091:Exons; D020869:Gene Expression Profiling; D023061:Gene Order; D023281:Genomics / Q000379:methods; D006801:Humans; D007378:Interleukins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007438:Introns; D015201:Meta-Analysis as Topic; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D040901:Proteomics / Q000379:methods; D016415:Sequence Alignment; D014714:Vertebrates
D016207:Cytokines; C529076:IL34 protein, human; D007378:Interleukins