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  • American Society of Hematology  (1)
  • Hindawi  (1)
  • 2015-2019  (2)
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  • 1
    Publikationsdatum: 2016-12-02
    Beschreibung: Dickkopf-3 (DKK-3) is a Wnt signaling antagonist, and DKK3 inactivation is associated with poor prognosis in various solid tumors and hematologic malignancies. Epigenetic hypermethylation has been implicated in downregulation of DKK3, but other regulatory mechanisms remain to be investigated. In this study, we examined DKK3 expression and the role of microRNA in the regulation of DKK3 in adult B-ALL. Our results showed low levels of DKK3 expression in Nalm-6 and BALL-1 cell lines, and leukemia cells from adult B-ALL patients. DKK3 expression was remarkably lower in the initial diagnosis and relapse samples than in the matched samples during remission. In addition to hypermethylation, low levels of DKK3 were associated with high expression of miR-708. This finding was similar to that in childhood ALL. The miR-708 was predicted to bind to the 3'-UTR of DKK3. By using miR-708 mimics, we found that miR-708 targets DKK3 to promote B-ALL cell proliferation through cell cycle promotion and apoptosis inhibition. The treatment with 5-aza-2'-deoxycytidine significantly increased DKK3 and decreased p-GSK3β, cyclin D1 and nuclear and cytoplasmic β-catenin protein expression. A synergistic effect was seen when the miR-708 inhibitor and 5-aza were used simultaneously. Although miR-708 was reported to either promote or suppress tumorigenecity in some solid tumors, our findings indicate that suppression of miR-708 increases DKK3 expression to inhibit the Wnt/β- catenin signaling pathway in B-ALL. Disclosures No relevant conflicts of interest to declare.
    Print ISSN: 0006-4971
    Digitale ISSN: 1528-0020
    Thema: Biologie , Medizin
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Publikationsdatum: 2017-01-01
    Beschreibung: Social influence analysis is important for many social network applications, including recommendation and cybersecurity analysis. We observe that the influence of community including multiple users outweighs the individual influence. Existing models focus on the individual influence analysis, but few studies estimate the community influence that is ubiquitous in online social network. A major challenge lies in that researchers need to take into account many factors, such as user influence, social trust, and user relationship, to model community-level influence. In this paper, aiming to assess the community-level influence effectively and accurately, we formulate the problem of modeling community influence and construct a community-level influence analysis model. It first eliminates the zombie fans and then calculates the user influence. Next, it calculates the user final influence by combining the user influence and the willingness of diffusing theme information. Finally, it evaluates the community influence by comprehensively studying the user final influence, social trust, and relationship tightness between intrausers of communities. To handle real-world applications, we propose a community-level influence analysis algorithm called CIAA. Empirical studies on a real-world dataset from Sina Weibo demonstrate the superiority of the proposed model.
    Print ISSN: 1076-2787
    Digitale ISSN: 1099-0526
    Thema: Informatik , Mathematik
    Publiziert von Hindawi
    Standort Signatur Erwartet Verfügbarkeit
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