The aim of the present study was to identify novel microrna (mirna) or long noncoding rna (lncrna) signatures of laryngeal cancer recurrence and to investigate the regulatory mechanisms associated with this malignancy. datasets of recurrent and nonrecurrent laryngeal cancer samples were downloaded from The cancer Genome atlas (TcGa) and the Gene expression omnibus database (GSe27020 and GSe25727) to examine differentially expressed mirnas (de-mirs), lncrnas (de-lncrs) and mrnas (deGs). mirna-mrna and lncrna-mirna networks were constructed by investigating the associations among these rnas in various databases. Subsequently, the interactions identified were combined into a competing endogenous rna (cerna) regulatory network. Feature genes in the miRNA-mRNA network were identified via topological analysis and a recursive feature elimination algorithm. a support vector machine (SVM) classifier was established using the betweenness centrality values in the mirna-mrna network, consisting of 32 optimal feature-coding genes. The classification effect was tested using two validation datasets. Furthermore, coding genes in the cerna network were examined via pathway enrichment analyses. in total, 21 de-lncrs, 507 DEGs and 55 DE-miRs were selected. The SVM classifier exhibited an accuracy of 94.05% (79/84) for sample classification prediction in the TcGa dataset, and 92.66 and 91.07% in the two validation datasets. The cerna regulatory network comprised 203 nodes, corresponding to mrnas, mirnas and lncrnas, and 346 lines, corresponding to the interactions among rnas. in particular, the interactions with the highest scores were Hla complex group 4 (HcG4)-mir-33b, HoX transcript antisense rna (HoTair)-mir-1-MaGe family member a2 (MaGea2), eMX2 opposite strand/antisense rna (eMX2oS)-mir-124-calcitonin related polypeptide α (calca) and eMX2oS-mir-124-γ-aminobutyric acid type a receptor γ2 subunit (GaBrG2). Gene enrichment analysis of the genes in the ceRNA network identified that 11 pathway terms and 16 molecular function terms were significantly enriched. The SVM classifier based on 32 feature coding genes exhibited high accuracy in the classification of laryngeal cancer samples. mir-1, mir-33b, mir-124, HoTair, HcG4 and eMX2oS may be novel biomarkers of recurrent laryngeal cancer, and HcG4-mir-33b, HoTair-mir-1-MaGea2 and eMX2oS-mir-124-calca/GaBrG2 may be associated with the molecular mechanisms regulating recurrent laryngeal cancer.

The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two‐stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT‐PCR analysis (qRT‐PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10−19). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC.

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BackgroundNasopharyngeal carcinoma (NPC) is a multi-factorial malignancy closely associated with environmental factors, genetic factors and Epstein-Barr virus infection. Human leukocyte antigen (HLA) complex, specially the region near HLA-A locus, was regarded as a major candidate region bearing NPC genetic susceptibility loci in many previous studies including two recent genome-wide association (GWA) studies. To provide further evidence for the NPC susceptibility in the region near HLA-A locus based on other previous studies, we carried out a two-stage hospital-based case control association study including 535 sporadic NPC patients and 525 cancer-free control subjects from Guangdong, a high prevalence area of NPC in China.Methods38 tag SNPs were initially selected by Heploview from the segment around HLA-A locus (from D6S211 to D6S510) and genotyped on GenomeLab SNPstream platform in 206 cases and 180 controls in the stage 1. Subsequently, the stage 1 significant SNPs and 17 additional SNPs were examined on another platform (Sequenom iPlex Assay) in another independent set of study population including 329 cases and 345 controls.ResultsTotally eight SNPs from the segment from D6S211 to D6S510 within HLA complex were found to be significantly associated with NPC. Two of the most significant SNPs (rs9260734 and rs2517716) located near to HLA-A and HCG9 respectively were in strong LD with some other SNPs of this region reported by two previous GWA studies. Meanwhile, Meanwhile, novel independent susceptibility loci (rs9404952, Pcombined = 6.6 × 10-5, OR combined = 1.45) was found to be close to HLA-G.ConclusionTherefore, our present study supports that the segment from D6S211 to D6S510 in HLA complex region might contain NPC susceptibility loci which indeed needs to be fully investigated in the future.

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