Deciphering c-MYC-regulated genes in two distinct tissues

Robson, Samuel; Ward, Lesley A.; Brown, Helen; Turner, Heather; Hunter, Ewan; Pelengaris, Stella; Khan, Michael

doi:10.1186/1471-2164-12-476

Cited by 18 publications

(17 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In support of these findings, we observed a marked increase in Igf1 and Igf2 gene expression at gestational day 20 as a result of growth restriction, with a concomitant increase in cardiac Cmyc mRNA expression. There is evidence that variable expression of Igf1 can influence expression of downstream Cmyc in murine skin cells, pancreatic beta-cells (35) and human preadipocytes (14). However, the increased cardiac Bcl2 gene expression we observed at gestational day 20 is contradictory to previous literature, which showed overexpression of Igf1 in mice can attenuate aging-induced increases in cardiac Bcl2 gene expression (23).…”

Section: Discussioncontrasting

confidence: 91%

Normal lactational environment restores cardiomyocyte number after uteroplacental insufficiency: implications for the preterm neonate

Black

Siebel

Gezmish

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

A reduced complement of cardiomyocytes in early life can adversely affect life-long cardiac functional reserve. In the present study, using a cross-fostering approach in rats, we examined the contributions of the prenatal and postnatal environments in the programming of cardiomyocyte growth. Rat dams underwent either bilateral uterine vessel ligation (Restricted) or sham surgery (Control) on day 18 of gestation. One day after birth, Control and Restricted pups were cross-fostered onto Control (normal lactation) or Restricted (impaired lactation due to impaired mammary gland formation) mothers. In male offspring, genes involved in cardiomyocyte differentiation, proliferation, hypertrophy and apoptosis were examined at gestational day 20 and postnatal days 1 and 7 to assess effects on cardiomyocyte growth. At postnatal day 7 cardiomyocyte number was determined stereologically. Offspring were examined at age 6 mo for evidence of hypertension and pathological cardiac gene expression. There was an increase in Igf1 and Igf2 mRNA expression in hearts of Restricted pups at gestational day 20. At postnatal day 7, Agtr1a and Agtr1b mRNA expression as well as Bcl2 and Cmyc were elevated in all hearts from offspring that were prenatally or postnatally growth restricted. There was a significant reduction (-29%) in cardiomyocyte number in the Restricted-on-Restricted group. Importantly, this deficit was prevented by optimization of postnatal nutrition (in the Restricted-on-Control group). At 6 mo, blood pressure was significantly elevated in the Restricted-on-Restricted group, but there was no difference in expression of the cardiac hypertrophy, remodeling or angiogenic genes across groups. In conclusion, the findings reveal a critical developmental window, when cardiomyocytes are still proliferating, whereby improved neonatal nutrition has the capacity to restore cardiomyocyte number to normal levels. These findings are of particular relevance to the preterm infant who is born at a time when cardiomyocytes are immature and still dividing.

show abstract

Section: Discussioncontrasting

confidence: 91%

Normal lactational environment restores cardiomyocyte number after uteroplacental insufficiency: implications for the preterm neonate

Black

Siebel

Gezmish

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…C-myc has been shown to negatively regulate e-cadherin through activating the transcription of microRNA-9 in breast cancer cells [19], which was consistent with our observation. In addition, c-Myc can induce expression of Cyclin D1 to promote cell cycle progression in multiple systems [20,21], and functional interactions between c-Myc and cylclin D1 play a critical role in tumor initiation, progression and response to chemotherapy [22]. Therefore, we suspect that our observation that knockdown of ZXF2 led to down regulation of Cyclin D1 could also be c-Myc dependent.…”

Section: Discussionmentioning

confidence: 98%

Overexpression of Long Non-Coding RNA ZXF2 Promotes Lung Adenocarcinoma Progression Through c-Myc Pathway

Yang

Wang

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Objective: To investigate the expression of long non-coding RNA ZXF2 in lung adenocarcinoma tissues and its effect on cell proliferation, migration and invasion. Methods: Forty pairs of cancerous and adjacent non-cancerous lung adenocarcinoma specimens were collected for the studies. Quantitative real-time PCR was used to analyze the expression of ZXF2 in tumor tissues and adjacent normal tissues. The expression of ZXF2 was correlated with patients' clinico-pathological data. Molecular pathway controlled by ZXF2 was explored by using small interfering RNA (siRNA) technology. CCK-8 cell proliferation assay, flow cytometry analysis and transwell assays were used to evaluate cell proliferation, migration and invasion. Results: The expression of ZXF2 was 2 fold or higher in 27 out of 40 (67.5%) cases of lung adenocarcinoma specimens than that in non-cancerous tissues (P<0.05). The relative expression level of ZXF2 was positively correlated with tumor lymph node metastasis (χ²=8.485, P<0.05) and poor prognosis of the patients (p=0.0217). In order to explore the molecular mechanisms of ZXF2 mediated tumor progression, ZXF2 expression was inhibited by siRNA in A549 cells, a highly aggressive and metastatic lung adenocarcinoma cell line. We found that siRNA-ZXF2 treatment inhibited cell proliferation (P<0.01) leading to cell cycle arrest (P<0.01). The cell migration and invasion were suppressed by siRNA-ZXF2 treatment (P<0.01). Further biochemical studies revealed that the knockdown of ZXF2 led to down regulation of c-Myc signaling. Conclusion: ZXF2 was overexpressed in lung adenocarcinoma tissues and the high expression of ZXF was closely related to tumor progression through c-Myc related pathway. Given the fact that both ZXF2 and c-Myc are located in the same chromosome 8q24.2 loci, the potential interaction between ZXF2 and c-Myc might be a novel target for treatment of lung adenocarcinoma.

show abstract

“…3). Of note, Myc is also an oxidative stress-responsive gene (Elouil et al 2005, Jonas et al 2009) that has been implicated in β-cell dedifferentiation (Jonas et al 2001, Laybutt et al 2002c, Pascal et al 2008, Robson et al 2011. On the other hand, it has been proposed that Myc expression is negatively regulated by PDX1 (Chen et al 2007).…”

Section: Downregulation Of Insulin Gene Expressionmentioning

confidence: 99%

Mechanisms of β-cell dedifferentiation in diabetes: recent findings and future research directions

Bensellam

Jonas

Laybutt

2018

Journal of Endocrinology

206

171

View full text Add to dashboard Cite

Like all the cells of an organism, pancreatic β-cells originate from embryonic stem cells through a complex cellular process termed differentiation. Differentiation involves the coordinated and tightly controlled activation/repression of specific effectors and gene clusters in a time-dependent fashion thereby giving rise to particular morphological and functional cellular features. Interestingly, cellular differentiation is not a unidirectional process. Indeed, growing evidence suggests that under certain conditions, mature β-cells can lose, to various degrees, their differentiated phenotype and cellular identity and regress to a less differentiated or a precursor-like state. This concept is termed dedifferentiation and has been proposed, besides cell death, as a contributing factor to the loss of functional β-cell mass in diabetes. β-cell dedifferentiation involves: (1) the downregulation of β-cell-enriched genes, including key transcription factors, insulin, glucose metabolism genes, protein processing and secretory pathway genes; (2) the concomitant upregulation of genes suppressed or expressed at very low levels in normal β-cells, the β-cell forbidden genes; and (3) the likely upregulation of progenitor cell genes. These alterations lead to phenotypic reconfiguration of β-cells and ultimately defective insulin secretion. While the major role of glucotoxicity in β-cell dedifferentiation is well established, the precise mechanisms involved are still under investigation. This review highlights the identified molecular mechanisms implicated in β-cell dedifferentiation including oxidative stress, endoplasmic reticulum (ER) stress, inflammation and hypoxia. It discusses the role of Foxo1, Myc and inhibitor of differentiation proteins and underscores the emerging role of non-coding RNAs. Finally, it proposes a novel hypothesis of β-cell dedifferentiation as a potential adaptive mechanism to escape cell death under stress conditions.

show abstract

Deciphering c-MYC-regulated genes in two distinct tissues

Cited by 18 publications

References 108 publications

Normal lactational environment restores cardiomyocyte number after uteroplacental insufficiency: implications for the preterm neonate

Normal lactational environment restores cardiomyocyte number after uteroplacental insufficiency: implications for the preterm neonate

Overexpression of Long Non-Coding RNA ZXF2 Promotes Lung Adenocarcinoma Progression Through c-Myc Pathway

Mechanisms of β-cell dedifferentiation in diabetes: recent findings and future research directions

Contact Info

Product

Resources

About