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Regulation of Human CYP2D6
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
Several GWASs of liver biopsy specimens from patients with chronic hepatitis C have been reported (Aghemo and Colombo 2013; Asselah et al. 2005; Duggal et al. 2013; Patin et al. 2012; Tanaka et al. 2009; Urabe et al. 2013). Upregulation of IL-6 and TNF-α and downregulation of CYP2E1 are observed as compared with normal liver patients (Asselah et al. 2005; Bieche et al. 2005). It is also shown that IL-6 and TNF-α levels in patients with liver fibrosis stages 2 to 4 are significantly higher than those in patients with stage 1 fibrosis only (Asselah et al. 2005). Two SNPs near the gene IL28B on chromosome 19 are strongly associated with null virological response to antiviral therapy in Japanese patients with hepatitis C (Tanaka et al. 2009). One recent GWAS has been performed in a large cohort of Japanese patients with hepatitis C viral infection using 780,650 SNPs (Patin et al. 2012). In the combined cohort of patients with hepatitis C, the SNPs rs16851720 on chromosome 3 and rs4374383 on chromosome 2 in patients are associated with fibrosis progression. The SNP rs16851720 is located within ring finger protein 7 (RNF7), which encodes an antioxidant that protects against apoptosis. RNF7 is a probable component of the SCF (SKP1-CULl-F-box protein) E3 ubiquitin ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction, and transcription (Mahrour et al. 2008; Sun and Li 2013; Tan et al. 2008). The SNP rs4374383, together with another replicated SNP rs9380516 on chromosome 6, is linked to the functionally related genes C-Mer proto-oncogene tyrosine kinase 1 (MERTK) and tubby-like protein 1 (TULPI), which encode factors involved in phagocytosis of apoptotic cells by macrophages (Patin et al. 2012). Mutations in MERTK have been associated with disruption of the retinal pigment epithelium phagocytosis pathway and onset of autosomal recessive retinitis pigmentosa (Cummings et al. 2013; Graham et al. 2014; Lemke 2013; Lemke and Rothlin 2008; van der Meer et al. 2014), where mutations in TULPI may be associated with juvenile retinitis pigmentosa and Leber congenital amaurosis-15 (Carroll et al. 2004; Ikeda et al. 2002; Mukhopadhyay and Jackson 2011; Weleber et al. 1993). This study has identified several susceptibility loci for hepatitis C virus–induced liver fibrosis, which are linked to genes that regulate apoptotic pathway and redox homeostasis involved in liver fibrosis.
Integrative transcriptome analysis identifies genes and pathways associated with enzalutamide resistance of prostate cancer
Published in The Aging Male, 2018
Subo Qian, Jia Xia, Hailong Liu, Yu Zhang, Lin Zhang, Yongjiang Yu
A number of the above pathways can be further explored. For instance, ubiquitin mediated proteolysis (hsa04120) was the top pathway enriched with sDEGs, but was not significantly enriched with rDEGs. A series of genes related to this pathway were generally up-regulated (e.g. PML, SOCS3, MID1, UBE2H, FBXO2, RNF7, VHL, HERC4, CUL5, UBE3B, and UBE2K) or down-regulated (e.g. UBE3C, PIAS2, UBE2D2, and UBE2I) upon enzalutamide treatment only in sensitive cell lines but not resistant ones (Figure 4). Such differences suggested that enzalutamide may exert antineoplastic effect in sensitive cell lines through the ubiquitin-proteasome system, which is abnormal in resistant cell lines and leads to enzalutamide resistance.
Identification of key genes and miRNA-mRNA regulatory networks associated with bone marrow immune microenvironment regulations in multiple myeloma by integrative bioinformatics analysis
Published in Hematology, 2022
Niluopaer Tuerxun, Jie Wang, Yu-ting Qin, Fang Zhao, Huan Wang, Jian-hua Qu, Md. Nazim Uddin, Jian-ping Hao
We inputted all DEGs into the STRING v11 to construct protein–protein interaction networks for identifying hub genes in MM. We identified 112 hub genes (degree of interaction ≥ 20) in MM that included 10 upregulated DEGs, and 102 downregulated DEGs (Figure 2A and Supplementary Table S5). The upregulated hub genes in MM included IGF1, IRF1, RPS28, UBA52, RPL32, RPS19, CDKN1A, RNF7, PSMB8, and CDKN2A. Some of the downregulated hub genes in MM are TP53, BRCA1, CCNB1, CDC20, PCNA, CDC6, BPTF, POLR2B, HDAC2, SMC1A, and MSH2. Furthermore, we identified the significant clusters of identified hub genes by using the Cytoscape plugin MCODE. The hub gene-associated five significant clusters in MM (Table 3, Figure 1(A, C, E, G, and H)). The functional enrichment analysis revealed that cluster 1 (Figure 1A) is associated with the enrichment of 20 KEGG pathways, including cell cycle, pathways in cancer, p53 signaling pathway, mismatch repair, DNA replication, bladder cancer, glioma, melanoma, chronic myeloid leukemia, small cell lung cancer, prostate cancer, homologous recombination, nucleotide excision repair, non-small cell lung cancer, pancreatic cancer, and TGF-beta signaling pathway (Figure 1B). Hub gene-associated cluster 2 (Figure 1C) is associated with the enrichment of 3 KEGG pathways (ubiquitin-mediated proteolysis, oocyte meiosis, and proteasome (Figure 1D)), and cluster 3 (Figure 1E) is related to the enrichment of 3 other KEGG pathways (cell cycle, nucleotide excision repair, and pancreatic cancer (Figure 1F)). It indicated that the hub genes-associated clusters are associated with the enrichment of cancer-related pathways in MM.