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

doi:10.3390/cancers13040825

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

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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 language	English
Article number	825
Pages (from-to)	1-18
Number of pages	18
Journal	Cancers
Volume	13
Issue number	4
DOIs	https://doi.org/10.3390/cancers13040825
Publication status	Published - 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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8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival
Martin, R. M.
1/10/20 → 30/09/25
Project: Research

Cite this

Kingshott, Georgina G ; Biernacka, Kalina M ; Sewell, Alex W ; Barker, Rachel M ; Zielinska, Hanna A ; Mccarthy, Kathryn ; Martin, Richard M ; Lane, J. Athene ; Rowe, Edward ; Oxley, Jon ; Holly, Jeff M. P. ; Perks, Claire M. / Alteration of Metabolic Conditions Impacts the Regulation of IGF-II/H19 Imprinting Status in Prostate Cancer. In: Cancers. 2021 ; Vol. 13, No. 4. pp. 1-18.

@article{b8002d4613494a2ab259a94a49a4ee1c,

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

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 {\textquoteleft}imprinted{\textquoteright} – 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.",

keywords = "IGF2, H19, imprinting, cancer, inflammatory markers",

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

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: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = feb,

day = "16",

doi = "10.3390/cancers13040825",

language = "English",

volume = "13",

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journal = "Cancers",

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}

Alteration of Metabolic Conditions Impacts the Regulation of IGF-II/H19 Imprinting Status in Prostate Cancer. / Kingshott, Georgina G ; Biernacka, Kalina M; Sewell, Alex W; Barker, Rachel M; Zielinska, Hanna A; Mccarthy, Kathryn; Martin, Richard M ; Lane, J. Athene; Rowe, Edward ; Oxley, Jon ; Holly, Jeff M. P.; Perks, Claire M.

In: Cancers, Vol. 13, No. 4, 825, 16.02.2021, p. 1-18.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Alteration of Metabolic Conditions Impacts the Regulation of IGF-II/H19 Imprinting Status in Prostate Cancer

AU - Kingshott, Georgina G

AU - Biernacka, Kalina M

AU - Sewell, Alex W

AU - Barker, Rachel M

AU - Zielinska, Hanna A

AU - Mccarthy, Kathryn

AU - Martin, Richard M

AU - Lane, J. Athene

AU - Rowe, Edward

AU - Oxley, Jon

AU - Holly, Jeff M. P.

AU - Perks, Claire M

N1 - 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.

PY - 2021/2/16

Y1 - 2021/2/16

N2 - 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.

AB - 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.

KW - IGF2

KW - H19

KW - imprinting

KW - cancer

KW - inflammatory markers

U2 - 10.3390/cancers13040825

DO - 10.3390/cancers13040825

M3 - Article (Academic Journal)

C2 - 33669311

VL - 13

SP - 1

EP - 18

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 4

M1 - 825

ER -

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

Abstract

Bibliographical note

Structured keywords

Keywords

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Projects

8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival

Cite this