Regulation of IGF2 transcript and protein expression by altered methylation in breast cancer

Shetty, Preetha J; Movva, Sireesha; Pasupuleti, Nagarjuna; Vedicherlla, Bhavani; Vattam, Kiran Kumar; Venkatasubramanian, Sambasivan; Ahuja, Y.R.; Hasan, Qurratulain

doi:10.1007/s00432-010-0890-z

Cited by 34 publications

(26 citation statements)

References 36 publications

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“…We found that the expression of several genes were influenced by HMGA1P7 including also genes involved in cancer progression such as Col6a3, Mki67, H19, Igf2, Gpx3 and Leprel1 3031323334353637. Indeed, oncomine analyses and tissue-microarray immunohistochemistry showed overexpression of COL6A3 in colorectal carcinomas that was significantly and directly correlated with Dukes stage, T stage, stage, recurrence and smoking status and then with a poor prognosis30.…”

Section: Discussionmentioning

confidence: 88%

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HMGA1P7-pseudogene regulates H19 and Igf2 expression by a competitive endogenous RNA mechanism

Martino

Forzati

Marfella

et al. 2016

Sci Rep

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Recent studies have revealed that pseudogene transcripts can function as competing endogenous RNAs, and thereby can also contribute to cancer when dysregulated. We have recently identified two pseudogenes, HMGA1P6 and HMGA1P7 for the HMGA1 gene whose overexpression has a critical role in cancer progression. These pseudogenes work as competitive endogenous RNA decoys for HMGA1 and other cancer related genes suggesting their role in carcinogenesis. Looking for new HMGA1 pseudogene ceRNAs, we performed RNA sequencing technology on mouse embryonic fibroblasts deriving from transgenic mice overexpressing HMGA1P7. Here, we report that HMGA1P7 mRNA sustains the H19 and Igf2 overexpression by acting as miRNA decoy. Lastly, the expression of HMGA1P7 was significantly correlated with H19 and IGF2 levels in human breast cancer thereby suggesting a role for HMGA1P7 deregulation in this neoplasia.

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Section: Discussionmentioning

confidence: 88%

“…To confirm whether HMGA1P7 works as miRNA sponge for the regulation of H19 and IGF2 expression levels also in human cancer, we evaluated the expression of H19, IGF2 and HMGA1P7 in a panel of breast carcinoma samples by qRT-PCR, since H19 and IGF2 have been reported to be overexpressed in this type of tumor3637. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

HMGA1P7-pseudogene regulates H19 and Igf2 expression by a competitive endogenous RNA mechanism

Martino

Forzati

Marfella

et al. 2016

Sci Rep

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“…This may also be occurring at other DMRs, if hypothesized co-regulation with other imprinted regions [37] can be demonstrated. Previous studies have reported an association between circulating IGF2 protein concentrations and high birth weight [46] as well as risk of obesity [47] and several cancers [48, 49] in adulthood, suggesting early exposures may contribute to the variation in birth weight via epigenetic alterations.…”

Section: Discussionmentioning

confidence: 99%

Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight

Hoyo

Fortner

Murtha

et al. 2012

Cancer Causes Control

102

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PurposeAltered methylation at Insulin-like Growth Factor 2 (IGF2) regulatory regions has previously been associated with obesity, and several malignancies including colon, esophageal, and prostate adenocarcinomas, presumably via changes in expression and/or loss of imprinting, but the functional significance of these DNA methylation marks have not been demonstrated in humans. We examined associations among DNA methylation at IGF2 differentially methylated regions (DMRs), circulating IGF2 protein concentrations in umbilical cord blood (UCB) and birth weight in newborns.MethodsQuestionnaire data were obtained from 300 pregnant women recruited between 2005 and 2009. UCB DNA methylation was measured by bisulfite pyrosequencing. UCB plasma concentrations of soluble IGF2 were measured by ELISA assays. Generalized linear regression models were used to examine the relationship between DMR methylation and IGF2 levels.ResultsLower IGF2 DMR methylation was associated with elevated plasma IGF2 protein concentrations (β = −9.87, p < 0.01); an association that was stronger in infants born to obese women (pre-pregnancy BMI > 30 kg/m2, β = −20.21, p < 0.0001). Elevated IGF2 concentrations were associated with higher birth weight (p < 0.0001) after adjusting for maternal race/ethnicity, pre-pregnancy BMI, cigarette smoking, gestational diabetes, and infant sex. These patterns of association were not apparent at the H19 DMR.ConclusionOur data suggest that variation in IGF2 DMR methylation is an important mechanism by which circulating IGF2 concentrations, a putative risk factor for obesity and cancers of the colon, esophagus, and prostate, are modulated; associations that may depend on pre-pregnancy obesity.

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“…Cadherins are usually downregulated in tumors, 64 whereas IGF2 is often overexpressed in many types of cancers and thought to be an oncogene. 70 Finally, our findings suggest the opportunity to identify additional luminal breast tumor markers. Expression of some of the 16 selected genes is usually weak or moderate in breast tissues (Human Protein Atlas).…”

Section: Discussionmentioning

confidence: 74%

Interaction between p53 and estradiol pathways in transcriptional responses to chemotherapeutics

Lion¹,

Bisio²,

Tebaldi³

et al. 2013

Cell Cycle

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Regulation of IGF2 transcript and protein expression by altered methylation in breast cancer

Abstract: Altered methylation of exonic CpG plays an important role in the enhanced transcription/expression of IGF2 in breast tumors. Methylation analysis of exon 9 CpG can be used as a biomarker for upregulation of IGF2 in breast tumor tissue and maybe developed as a diagnostic test in future.

Cited by 34 publications

References 36 publications

HMGA1P7-pseudogene regulates H19 and Igf2 expression by a competitive endogenous RNA mechanism

HMGA1P7-pseudogene regulates H19 and Igf2 expression by a competitive endogenous RNA mechanism

Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight

Interaction between p53 and estradiol pathways in transcriptional responses to chemotherapeutics

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