• English
    • العربية
  • العربية
  • Login
  • QU
  • QU Library
  •  Home
  • Communities & Collections
  • Help
    • Item Submission
    • Publisher policies
    • User guides
    • FAQs
  • About QSpace
    • Vision & Mission
View Item 
  •   Qatar University Digital Hub
  • Qatar University Institutional Repository
  • Academic
  • Faculty Contributions
  • College of Arts & Sciences
  • Mathematics, Statistics & Physics
  • View Item
  • Qatar University Digital Hub
  • Qatar University Institutional Repository
  • Academic
  • Faculty Contributions
  • College of Arts & Sciences
  • Mathematics, Statistics & Physics
  • View Item
  •      
  •  
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Characterization of regulatory sequences in alternative promoters of hypermethylated genes associated with tumor resistance to cisplatin

    Thumbnail
    View/Open
    Open Access Version of Record (469.0Kb)
    Date
    2014-11-27
    Author
    Ibrahim-Alobaide, Mohammed A.
    Abdelsalam, Abdelsalam G.
    Alobydi, Hytham
    Rasul, Kakil Ibrahim
    Zhang, Ruiwen
    Srivenugopal, Kalkunte S.
    ...show more authors ...show less authors
    Metadata
    Show full item record
    Abstract
    The development of cisplatin resistance in human cancers is controlled by multiple genes and leads to therapeutic failure. Hypermethylation of specific gene promoters is a key event in clinical resistance to cisplatin. Although the usage of multiple promoters is frequent in the transcription of human genes, the role of alternative promoters and their regulatory sequences have not yet been investigated in cisplatin resistance genes. In a new approach, we hypothesized that human cancers exploit the specific transcription factor-binding sites (TFBS) and CpG islands (CGIs) located in the alternative promoters of certain genes to acquire platinum drug resistance. To provide a useful resource of regulatory elements associated with cisplatin resistance, we investigated the TFBS and CGIs in 48 alternative promoters of 14 hypermethylated cisplatin resistance genes previously reported. CGIs prone to methylation were identified in 28 alternative promoters of 11 hypermethylated genes. The majority of alternative promoters harboring CGIs (93%) were clustered in one phylogenetic subclass, whereas the ones lacking CGIs were distributed in two unrelated subclasses. Regulatory sequences, initiator and TATA-532 prevailed over TATA-8 and were found in all the promoters. B recognition element (BRE) sequences were present only in alternative promoters harboring CGIs, but CCAAT and TAACC were found in both types of alternative promoters, whereas downstream promoter element sequences were significantly less frequent. Therefore, it was hypothesized that BRE and CGI sequences co-localized in alternative promoters of cisplatin resistance genes may be used to design molecular markers for drug resistance. A more extensive knowledge of alternative promoters and their regulatory elements in clinical resistance to cisplatin is likely to usher novel avenues for sensitizing human cancers to treatment.
    DOI/handle
    http://dx.doi.org/10.3892/mco.2014.468
    http://hdl.handle.net/10576/5020
    Collections
    • Mathematics, Statistics & Physics [‎792‎ items ]

    entitlement


    Qatar University Digital Hub is a digital collection operated and maintained by the Qatar University Library and supported by the ITS department

    Contact Us | Send Feedback
    Contact Us | Send Feedback | QU

     

     

    Home

    Submit your QU affiliated work

    Browse

    All of Digital Hub
      Communities & Collections Publication Date Author Title Subject Type Language Publisher
    This Collection
      Publication Date Author Title Subject Type Language Publisher

    My Account

    Login

    Statistics

    View Usage Statistics

    About QSpace

    Vision & Mission

    Help

    Item Submission Publisher policiesUser guides FAQs

    Qatar University Digital Hub is a digital collection operated and maintained by the Qatar University Library and supported by the ITS department

    Contact Us | Send Feedback
    Contact Us | Send Feedback | QU

     

     

    Video