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81.
Jing Lu Mingxin Wen Yurong Huang Xiuquan He Yunshan Wang Qi Wu Zengchun Li Andres Castellanos-Martin Mar Abad Juan J. Cruz-Hernandez Cesar A. Rodriguez Jesus Perez-Losada Jian-Hua Mao Guangwei Wei 《Epigenetics》2013,8(6):571-583
Recently, it has been suggested that C2ORF40 is a candidate tumor suppressor gene in breast cancer. However, the mechanism for reduced expression of C2ORF40 and its functional role in breast cancers remain unclear. Here we show that C2ORF40 is frequently silenced in human primary breast cancers and cell lines through promoter hypermethylation. C2ORF40 mRNA level is significantly associated with patient disease-free survival and distant cancer metastasis. Overexpression of C2ORF40 inhibits breast cancer cell proliferation, migration and invasion. By contrast, silencing C2ORF40 expression promotes these biological phenotypes. Bioinformatics and FACS analysis reveal C2ORF40 functions at G2/M phase by downregulation of mitotic genes expression, including UBE2C. Our results suggest that C2ORF40 acts as a tumor suppressor gene in breast cancer pathogenesis and progression and is a candidate prognostic marker for this disease. 相似文献
82.
Qinghong Wang Jijun Zhou Bei Zhang Zhiqiang Tian Jun Tang Yanhua Zheng Zemin Huang Yi Tian Zhengcai Jia Yan Tang Jennifer C. van Velkinburgh Qing Mao Xiuwu Bian Yifang Ping Bing Ni Yuzhang Wu 《PLoS pathogens》2013,9(6)
IL-23 regulates myriad processes in the innate and adaptive immune systems, and is a critical mediator of the proinflammatory effects exerted by Th17 cells in many diseases. In this study, we investigated whether and how hepatitis B virus (HBV) causes liver damage directly through the IL-23 signaling pathway. In biopsied liver tissues from HBV-infected patients, expression of both IL-23 and IL-23R was remarkably elevated. In vivo observations also indicated that the main sources of IL-23 were myeloid dendritic cells (mDCs) and macrophages. Analysis of in vitro differentiated immature DCs and macrophages isolated from healthy donors revealed that the HBV surface antigen (HBsAg) efficiently induces IL-23 secretion in a mannose receptor (MR)-dependent manner. Culture with an endosomal acidification inhibitor and the dynamin inhibitor showed that, upon binding to the MR, the HBsAg is taken up by mDCs and macrophages through an endocytosis mechanism. In contrast, although the HBV core antigen (HBcAg) can also stimulate IL-23 secretion from mDCs, the process was MR- and endocytosis-independent. In addition, IL-23 was shown to be indispensible for HBsAg-stimulated differentiation of naïve CD4+ T cells into Th17 cells, which were determined to be the primary source of IL-17 in HBV-infected livers. The cognate receptor, IL-17R, was found to exist on the hepatic stellate cells and mDCs, both of which might represent the potential target cells of IL-17 in hepatitis B disease. These data provide novel insights into a yet unrecognized mechanism of HBV-induced hepatitis, by which increases in IL-23 expression, through an MR/endocytosis-dependent or -independent manner, produce liver damage through the IL-23/IL-17 axis. 相似文献
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Xiao Na Wang Ze Song Li Yu Ren Tao Jiang Ya Qing Wang Min Chen Jun Zhang Jian Xiu Hao Yan Bo Wang Ri Na Sha Yi Huang Xiao Liu Jing Chu Hu Guang Qing Sun Hong Gang Li Cheng Liang Xiong Jun Xie Zhi Mao Jiang Zhi Ming Cai Jun Wang Jian Wang Vicki Huff Yao Ting Gui Fei Gao 《PLoS genetics》2013,9(8)
Azoospermia is one of the major reproductive disorders which cause male infertility in humans; however, the etiology of this disease is largely unknown. In the present study, six missense mutations of WT1 gene were detected in 529 human patients with non-obstructive azoospermia (NOA), indicating a strong association between WT1 mutation and NOA. The Wilms tumor gene, Wt1, is specifically expressed in Sertoli cells (SCs) which support spermatogenesis. To examine the functions of this gene in spermatogenesis, Wt1 was deleted in adult testis using Wt1flox and Cre-ERTM mice strains. We found that inactivation of Wt1 resulted in massive germ cell death and only SCs were present in most of the seminiferous tubules which was very similar to NOA in humans. In investigating the potential mechanism for this, histological studies revealed that the blood–testis barrier (BTB) was disrupted in Wt1 deficient testes. In vitro studies demonstrated that Wt1 was essential for cell polarity maintenance in SCs. Further studies found that the expression of cell polarity associated genes (Par6b and E-cadherin) and Wnt signaling genes (Wnt4, Wnt11) were downregulated in Wt1 deficient SCs, and that the expression of Par6b and E-cadherin was regulated by Wnt4. Our findings suggest that Wt1 is important in spermatogenesis by regulating the polarity of SCs via Wnt signaling pathway and that WT1 mutation is one of the genetic causes of NOA in humans. 相似文献
85.
Stephen E. Kaiser Yu Qiu Julie E. Coats Kai Mao Daniel J. Klionsky Brenda A. Schulman 《Autophagy》2013,9(5):778-780
Central to most forms of autophagy are two ubiquitin-like proteins (UBLs), Atg8 and Atg12, which play important roles in autophagosome biogenesis, substrate recruitment to autophagosomes, and other aspects of autophagy. Typically, UBLs are activated by an E1 enzyme that (1) catalyzes adenylation of the UBL C terminus, (2) transiently covalently captures the UBL through a reactive thioester bond between the E1 active site cysteine and the UBL C terminus, and (3) promotes transfer of the UBL C terminus to the catalytic cysteine of an E2 conjugating enzyme. The E2, and often an E3 ligase enzyme, catalyzes attachment of the UBL C terminus to a primary amine group on a substrate. Here, we summarize our recent work reporting the structural and mechanistic basis for E1-E2 protein interactions in autophagy. 相似文献
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88.
Lingling Wang Yufu Tang Shuo Liu Shitao Mao Yuan Ling Dan Liu Xiaoyu He Xiaoge Wang 《PloS one》2013,8(6)
Chronic obstructive pulmonary disease (COPD) has seriously impacted the health of individuals and populations. In this study, proton nuclear magnetic resonance (1H NMR)-based metabonomics combined with multivariate pattern recognition analysis was applied to investigate the metabolic signatures of patients with COPD. Serum and urine samples were collected from COPD patients (n = 32) and healthy controls (n = 21), respectively. Samples were analyzed by high resolution 1H NMR (600 MHz), and the obtained spectral profiles were then subjected to multivariate data analysis. Consistent metabolic differences have been found in serum as well as in urine samples from COPD patients and healthy controls. Compared to healthy controls, COPD patients displayed decreased lipoprotein and amino acids, including branched-chain amino acids (BCAAs), and increased glycerolphosphocholine in serum. Moreover, metabolic differences in urine were more significant than in serum. Decreased urinary 1-methylnicotinamide, creatinine and lactate have been discovered in COPD patients in comparison with healthy controls. Conversely, acetate, ketone bodies, carnosine, m-hydroxyphenylacetate, phenylacetyglycine, pyruvate and α-ketoglutarate exhibited enhanced expression levels in COPD patients relative to healthy subjects. Our results illustrate the potential application of NMR-based metabonomics in early diagnosis and understanding the mechanisms of COPD. 相似文献
89.
Zhen-Zhu Su Li-Juan Mao Na Li Xiao-Xiao Feng Zhi-Lin Yuan Li-Wei Wang Fu-Cheng Lin Chu-Long Zhang 《PloS one》2013,8(4)
The mutualism pattern of the dark septate endophyte (DSE) Harpophora oryzae in rice roots and its biocontrol potential in rice blast disease caused by Magnaporthe oryzae were investigated. Fluorescent protein-expressing H. oryzae was used to monitor the colonization pattern. Hyphae invaded from the epidermis to the inner cortex, but not into the root stele. Fungal colonization increased with root tissue maturation, showing no colonization in the meristematic zone, slight colonization in the elongation zone, and heavy colonization in the differentiation zone. H. oryzae adopted a biotrophic lifestyle in roots accompanied by programmed cell death. Real-time PCR facilitated the accurate quantification of fungal growth and the respective plant response. The biocontrol potential of H. oryzae was visualized by inoculation with eGFP-tagged M. oryzae in rice. H. oryzae protected rice from M. oryzae root invasion by the accumulation of H2O2 and elevated antioxidative capacity. H. oryzae also induced systemic resistance against rice blast. This systemic resistance was mediated by the OsWRKY45-dependent salicylic acid (SA) signaling pathway, as indicated by the strongly upregulated expression of OsWRKY45. The colonization pattern of H. oryzae was consistent with the typical characteristics of DSEs. H. oryzae enhanced local resistance by reactive oxygen species (ROS) and high antioxidative level and induced OsWRKY45-dependent SA-mediated systemic resistance against rice blast. 相似文献
90.