NFYAv1 is a Tumor-Promoting Transcript Associated with Poor Prognosis of Hepatocellular Carcinoma.

BACKGROUND Nuclear Transcription Factor Y Subunit Alpha (NFYA), together with NFYB and NFYC, form a sequence-specific heterotrimeric nuclear transcription factor (NFY), but their functional role in hepatocellular carcinoma (HCC) is still unclear. In this study, we explored the association between the NFY subunit genes and the survival of primary hepatocellular carcinoma (HCC) patients in The Cancer Genome Atlas (TCGA). The transcript-specific effect on HCC cell growth was studied. MATERIAL AND METHODS RNA-seq data from the Genotype-Tissue Expression Project (GTEx) and TCGA were analyzed in combination. In vitro cellular and molecular studies were conducted using SK-Hep-1 and Hep3B cells. Pearson's correlation coefficients were calculated to assess correlations. Welch's unpaired t test and one-way ANOVA with post hoc Tukey's multiple comparisons were performed. Kaplan-Meier (K-M) survival curves were assessed by conducting log-rank (Mantel-Cox) test. RESULTS NFYA was the only prognosis-related gene. Among the 2 splicing transcripts of NFYA, the long isoform (NFYAv1, NM_002505.5) but not the short-form (NFYAv2, NM_021705.4) was significantly associated with worse progression-free survival (PFS) (high [n=179] vs low [n=179], HR: 1.657, 95% CI: 1.228-2.235, P<0.001) and disease-specific survival (DSS) (high [n=175] vs low [n=175], HR: 1.986, 95% CI: 1.269-3.108, P<0.001) in HCC patients. GO/KEGG analysis in TCGA confirmed that NFYAv1 and NFYAv2 co-expressed (|Pearson's r|≥0.6) genes in primary HCC patients were enriched in quite different GO/KEGG terms. NFYAv1 knockdown significantly decreased cell viability and increased G0/G1 cell cycle arrest. The shRNA only targeting NFYAv1 had a significantly stronger growth-inhibiting effect than the shRNA targeting both NFYAv1 and NFYAv2. CONCLUSIONS This study showed that NFYAv1 is a tumor-promoting transcript associated with poor prognosis of HCC.

Association between polymorphisms of cytokine genes and diabetic nephropathy: A comprehensive systematic review and meta-analysis.

AIM: Diabetic nephropathy (DN) is one of the microvascular complications of diabetes, leading to renal failure. In this study, we sought to systematically investigate the cytokine gene polymorphisms association with DN. METHODS: A structured bibliographic search on PubMed, Scopus, and EMBASE databases has been performed to identify related papers. The odds ratio and corresponding 95% confidence intervals (CIs) were calculated to estimate the association. RESULTS: Overall, the pooled results showed that the dominant models of TNF-α rs1800629, IL-1ß rs16944, IL-8 rs4073, and IL-10 rs1800896 were associated with increased susceptibility to DN. Also, the pooled analyses of the mutant allele vs wild allele of TNF-α rs1800629, rs1799964, IL-1ß rs16944, and IL-8 rs4073 were associated with increased susceptibility to DN. Rs1800629, rs16944, rs4073, and rs1800896 polymorphisms were significantly associated with DN susceptibility, suggesting its potential use as a genetic risk marker in the population.