Alteration of Metabolic Conditions Impacts the Regulation of IGF-II/H19 Imprinting Status in Prostate Cancer
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/H...
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Format: | Article |
Language: | English |
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MDPI AG
2021-02-01
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Series: | Cancers |
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Online Access: | https://www.mdpi.com/2072-6694/13/4/825 |
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doaj-4c8db63ee1144af2b88c2c73be734184 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Georgina Kingshott Kalina Biernacka Alex Sewell Paida Gwiti Rachel Barker Hanna Zielinska Amanda Gilkes Kathryn McCarthy Richard M. Martin J. Athene Lane Lucy McGeagh Anthony Koupparis Edward Rowe Jon Oxley Jeff M. P. Holly Claire M. Perks |
spellingShingle |
Georgina Kingshott Kalina Biernacka Alex Sewell Paida Gwiti Rachel Barker Hanna Zielinska Amanda Gilkes Kathryn McCarthy Richard M. Martin J. Athene Lane Lucy McGeagh Anthony Koupparis Edward Rowe Jon Oxley Jeff M. P. Holly Claire M. Perks Alteration of Metabolic Conditions Impacts the Regulation of IGF-II/H19 Imprinting Status in Prostate Cancer Cancers IGF2 H19 imprinting cancer inflammatory markers |
author_facet |
Georgina Kingshott Kalina Biernacka Alex Sewell Paida Gwiti Rachel Barker Hanna Zielinska Amanda Gilkes Kathryn McCarthy Richard M. Martin J. Athene Lane Lucy McGeagh Anthony Koupparis Edward Rowe Jon Oxley Jeff M. P. Holly Claire M. Perks |
author_sort |
Georgina Kingshott |
title |
Alteration of Metabolic Conditions Impacts the Regulation of IGF-II/H19 Imprinting Status in Prostate Cancer |
title_short |
Alteration of Metabolic Conditions Impacts the Regulation of IGF-II/H19 Imprinting Status in Prostate Cancer |
title_full |
Alteration of Metabolic Conditions Impacts the Regulation of IGF-II/H19 Imprinting Status in Prostate Cancer |
title_fullStr |
Alteration of Metabolic Conditions Impacts the Regulation of IGF-II/H19 Imprinting Status in Prostate Cancer |
title_full_unstemmed |
Alteration of Metabolic Conditions Impacts the Regulation of IGF-II/H19 Imprinting Status in Prostate Cancer |
title_sort |
alteration of metabolic conditions impacts the regulation of igf-ii/h19 imprinting status in prostate cancer |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-02-01 |
description |
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 imprinting 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. We observed disruption of imprinting behaviour, in vitro<i>,</i> with a significant increase in IGF-II and a reciprocal decrease in H19 mRNA; the increased mRNA was not translated into peptides. 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. Our findings show that type 2 diabetes and/or obesity, can directly affect regulation growth factors involved in carcinogenesis, indirectly suggesting a modification of lifestyle habits may reduce cancer risk. |
topic |
IGF2 H19 imprinting cancer inflammatory markers |
url |
https://www.mdpi.com/2072-6694/13/4/825 |
work_keys_str_mv |
AT georginakingshott alterationofmetabolicconditionsimpactstheregulationofigfiih19imprintingstatusinprostatecancer AT kalinabiernacka alterationofmetabolicconditionsimpactstheregulationofigfiih19imprintingstatusinprostatecancer AT alexsewell alterationofmetabolicconditionsimpactstheregulationofigfiih19imprintingstatusinprostatecancer AT paidagwiti alterationofmetabolicconditionsimpactstheregulationofigfiih19imprintingstatusinprostatecancer AT rachelbarker alterationofmetabolicconditionsimpactstheregulationofigfiih19imprintingstatusinprostatecancer AT hannazielinska alterationofmetabolicconditionsimpactstheregulationofigfiih19imprintingstatusinprostatecancer AT amandagilkes alterationofmetabolicconditionsimpactstheregulationofigfiih19imprintingstatusinprostatecancer AT kathrynmccarthy alterationofmetabolicconditionsimpactstheregulationofigfiih19imprintingstatusinprostatecancer AT richardmmartin alterationofmetabolicconditionsimpactstheregulationofigfiih19imprintingstatusinprostatecancer AT jathenelane alterationofmetabolicconditionsimpactstheregulationofigfiih19imprintingstatusinprostatecancer AT lucymcgeagh alterationofmetabolicconditionsimpactstheregulationofigfiih19imprintingstatusinprostatecancer AT anthonykoupparis alterationofmetabolicconditionsimpactstheregulationofigfiih19imprintingstatusinprostatecancer AT edwardrowe alterationofmetabolicconditionsimpactstheregulationofigfiih19imprintingstatusinprostatecancer AT jonoxley alterationofmetabolicconditionsimpactstheregulationofigfiih19imprintingstatusinprostatecancer AT jeffmpholly alterationofmetabolicconditionsimpactstheregulationofigfiih19imprintingstatusinprostatecancer AT clairemperks alterationofmetabolicconditionsimpactstheregulationofigfiih19imprintingstatusinprostatecancer |
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1724265889379909632 |
spelling |
doaj-4c8db63ee1144af2b88c2c73be7341842021-02-17T00:02:41ZengMDPI AGCancers2072-66942021-02-011382582510.3390/cancers13040825Alteration of Metabolic Conditions Impacts the Regulation of IGF-II/H19 Imprinting Status in Prostate CancerGeorgina Kingshott0Kalina Biernacka1Alex Sewell2Paida Gwiti3Rachel Barker4Hanna Zielinska5Amanda Gilkes6Kathryn McCarthy7Richard M. Martin8J. Athene Lane9Lucy McGeagh10Anthony Koupparis11Edward Rowe12Jon Oxley13Jeff M. P. Holly14Claire M. Perks15IGF & Metabolic Endocrinology Group, Translational Health Sciences, Bristol Medical School, Learning & Research Building, Southmead Hospital, Bristol BS10 5NB, UKIGF & Metabolic Endocrinology Group, Translational Health Sciences, Bristol Medical School, Learning & Research Building, Southmead Hospital, Bristol BS10 5NB, UKDepartment of Cellular Pathology, North Bristol NHS Trust, Southmead Hospital, Bristol BS10 5NB, UKDepartment of Cellular Pathology, North Bristol NHS Trust, Southmead Hospital, Bristol BS10 5NB, UKIGF & Metabolic Endocrinology Group, Translational Health Sciences, Bristol Medical School, Learning & Research Building, Southmead Hospital, Bristol BS10 5NB, UKIGF & Metabolic Endocrinology Group, Translational Health Sciences, Bristol Medical School, Learning & Research Building, Southmead Hospital, Bristol BS10 5NB, UKDepartment of Haematology, Cardiff University, Heath Park, Cardiff CF14 4XN, UKDepartment of Surgery, Department of Medicine, Southmead Hospital, Bristol BS10 5NB, UKPopulation Health Sciences, Bristol Medical School, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UKBristol Randomised Trials Collaboration, Population Health Sciences, Bristol Medical School, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UKSupportive Cancer Care Research Group, Faculty of Health and Life Sciences, Oxford Institute of Nursing, Midwifery and Allied Health Research, Oxford Brookes University, Jack Straws Lane, Marston, Oxford OX3 0FL, UKDepartment of Urology, Bristol Urological Institute, Southmead Hospital, Bristol BS10 5NB, UKDepartment of Urology, Bristol Urological Institute, Southmead Hospital, Bristol BS10 5NB, UKDepartment of Cellular Pathology, North Bristol NHS Trust, Southmead Hospital, Bristol BS10 5NB, UKIGF & Metabolic Endocrinology Group, Translational Health Sciences, Bristol Medical School, Learning & Research Building, Southmead Hospital, Bristol BS10 5NB, UKIGF & Metabolic Endocrinology Group, Translational Health Sciences, Bristol Medical School, Learning & Research Building, Southmead Hospital, Bristol BS10 5NB, UKProstate 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 imprinting 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. We observed disruption of imprinting behaviour, in vitro<i>,</i> with a significant increase in IGF-II and a reciprocal decrease in H19 mRNA; the increased mRNA was not translated into peptides. 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. Our findings show that type 2 diabetes and/or obesity, can directly affect regulation growth factors involved in carcinogenesis, indirectly suggesting a modification of lifestyle habits may reduce cancer risk.https://www.mdpi.com/2072-6694/13/4/825IGF2H19imprintingcancerinflammatory markers |