IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms15921.html
   My bibliography  Save this article

Alternative splicing promotes tumour aggressiveness and drug resistance in African American prostate cancer

Author

Listed:
  • Bi-Dar Wang

    (School of Medicine and Health Sciences, The George Washington University
    School of Pharmacy and Health Professions, University of Maryland Eastern Shore)

  • Kristin Ceniccola

    (School of Medicine and Health Sciences, The George Washington University)

  • SuJin Hwang

    (Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University)

  • Ramez Andrawis

    (School of Medicine and Health Sciences, The George Washington University)

  • Anelia Horvath

    (School of Medicine and Health Sciences, The George Washington University)

  • Jennifer A. Freedman

    (Duke University Medical Center)

  • Jacqueline Olender

    (School of Medicine and Health Sciences, The George Washington University)

  • Stefan Knapp

    (University of Oxford
    Structural Genomics Consortium, University of Oxford)

  • Travers Ching

    (Cancer Epidemiology Program, University of Hawaii Cancer Center)

  • Lana Garmire

    (Cancer Epidemiology Program, University of Hawaii Cancer Center)

  • Vyomesh Patel

    (Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health)

  • Mariano A. Garcia-Blanco

    (The University of Texas Medical Branch at Galveston)

  • Steven R. Patierno

    (Duke University Medical Center)

  • Norman H. Lee

    (School of Medicine and Health Sciences, The George Washington University)

Abstract

Clinical challenges exist in reducing prostate cancer (PCa) disparities. The RNA splicing landscape of PCa across racial populations has not been fully explored as a potential molecular mechanism contributing to race-related tumour aggressiveness. Here, we identify novel genome-wide, race-specific RNA splicing events as critical drivers of PCa aggressiveness and therapeutic resistance in African American (AA) men. AA-enriched splice variants of PIK3CD, FGFR3, TSC2 and RASGRP2 contribute to greater oncogenic potential compared with corresponding European American (EA)-expressing variants. Ectopic overexpression of the newly cloned AA-enriched variant, PIK3CD-S, in EA PCa cell lines enhances AKT/mTOR signalling and increases proliferative and invasive capacity in vitro and confers resistance to selective PI3Kδ inhibitor, CAL-101 (idelalisib), in mouse xenograft models. High PIK3CD-S expression in PCa specimens associates with poor survival. These results highlight the potential of RNA splice variants to serve as novel biomarkers and molecular targets for developmental therapeutics in aggressive PCa.

Suggested Citation

  • Bi-Dar Wang & Kristin Ceniccola & SuJin Hwang & Ramez Andrawis & Anelia Horvath & Jennifer A. Freedman & Jacqueline Olender & Stefan Knapp & Travers Ching & Lana Garmire & Vyomesh Patel & Mariano A. G, 2017. "Alternative splicing promotes tumour aggressiveness and drug resistance in African American prostate cancer," Nature Communications, Nature, vol. 8(1), pages 1-15, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15921
    DOI: 10.1038/ncomms15921
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms15921
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms15921?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Thanh Nguyen & Dhivya Sridaran & Surbhi Chouhan & Cody Weimholt & Audrey Wilson & Jingqin Luo & Tiandao Li & John Koomen & Bin Fang & Nagireddy Putluri & Arun Sreekumar & Felix Y. Feng & Kiran Mahajan, 2023. "Histone H2A Lys130 acetylation epigenetically regulates androgen production in prostate cancer," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15921. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.