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, 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.