Alteration of Metabolic Conditions Impacts the Regulation of IGF-II/H19 Imprinting Status in Prostate Cancer

Georgina G Kingshott*, Kalina M Biernacka*, Alex W Sewell, Rachel M Barker, Hanna A Zielinska, Kathryn Mccarthy, Richard M Martin, J. Athene Lane, Edward Rowe, Jon Oxley, Jeff M. P. Holly, Claire M Perks

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

1 Citation (Scopus)
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Abstract

Prostate cancer is the second major cause of male cancer deaths. Obesity, type 2 diabetes, and cancer risk are linked. Insulin-like growth factor II (IGF-II) is involved in numerous cellular events, including proliferation and survival. The IGF-II gene shares its locus with the lncRNA, H19. IGF-II/H19 was the first gene to be identified as being ‘imprinted’ – where the paternal copy is not transcribed – a silencing phenomenon lost in many cancer types. We disrupted im-printing behaviour in vitro by altering metabolic conditions and quantified it using RFLP, qPCR and pyrosequencing; changes to peptide were measured using RIA. Prostate tissue samples were analysed using ddPCR, pyrosequencing and IHC. We compared with in silico data, provided by TGCA on the cBIO Portal. Disruption of imprinting behaviour, in vitro, occurs at the molecular level with no changes to peptide. In vivo, most specimens retained imprinting status apart from a small subset which showed reduced imprinting. A positive correlation was seen between IGF-II and H19 mRNA expression, which concurred with findings of larger Cancer Genome Atlas (TGCA) cohorts. This positive correlation did not affect IGF-II peptide. Type 2 diabetes and / or obesity directly affect regulation growth factors involved in carcinogenesis.
Original languageEnglish
Article number825
Pages (from-to)1-18
Number of pages18
JournalCancers
Volume13
Issue number4
DOIs
Publication statusPublished - 16 Feb 2021

Bibliographical note

Funding Information:
Funding: This research was funded by Cancer Research UK (C18281/A29019): The Integrative Cancer Epidemiology Programme: Towards improved causal evidence and enhanced predication of cancer risk and survival: The APC was funded by the Bristol Biomedical Research Centre (BRC) and the National Institute for Health Research Bristol (NIHR) partnership.

Funding Information:
Acknowledgments: The research was supported by the NIHR Bristol Nutrition Biomedical Research Unit based at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. The views expressed are those of the authors and not necessarily those of the NHS, the University of Bristol, the NIHR or the Department of Health and Social Care. The work was also supported by Cancer Research UK: The Integrative Cancer Epidemiology Programme: Towards improved causal evidence and enhanced predication of cancer risk and survival: C18281/A29019.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Structured keywords

  • ICEP

Keywords

  • IGF2
  • H19
  • imprinting
  • cancer
  • inflammatory markers

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