Epigenetic control of EMT/MET dynamics: HNF4α impacts DNMT3s through miRs-29

Cicchini, Carla; Nonno, Valeria de; Battistelli, Cecilia; Cozzolino, Angela Maria; Puzzonia, Marco De Santis; Ciafrè, Silvia Anna; Brocker, Chad; Gonzalez, Frank J.; Amicone, Laura; Tripodi, Marco

doi:10.1016/j.bbagrm.2015.05.005

Cited by 63 publications

(58 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As in the Patterns, CREB1 was a predicted upstream regulator in PFC, NAc, BLA, and vHIP of genes associated with AI (Figure 5J). HNF4A was also a predicted upstream regulator of genes associated with AI and was one of two upstream regulators (TCF7L2) predicted for both Patterns B and C. HNF4A is implicated in epigenetic mechanisms (49–52) and dendritic spine morphology (51). While expression of Hnf4a was not detected in our sequencing data, other NRs were.…”

Section: Discussionmentioning

confidence: 99%

Cocaine Self-administration Alters Transcriptome-wide Responses in the Brain’s Reward Circuitry

Walker

Cates

Loh

et al. 2018

Biological Psychiatry

155

201

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Cocaine Self-administration Alters Transcriptome-wide Responses in the Brain’s Reward Circuitry

Walker

Cates

Loh

et al. 2018

Biological Psychiatry

155

201

View full text Add to dashboard Cite

show abstract

“…Additionally, miR-33a and miR-181b inhibitors reduce collagen type I and α-SMA expression in HSCs [21,32]. Moreover, published reports demonstrate that PTEN expression is tightly regulated by miR-29b in addition to DNMT3B [33]. However, how adiponectin modulates PTEN promoter methylation and miR-29b expression has not yet been fully described.…”

Section: Introductionmentioning

confidence: 99%

Adiponectin inhibits hepatic stellate cell activation by targeting the PTEN/AKT pathway

Kumar¹,

Raeman²,

Chopyk³

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

Adiponectin inhibits hepatic stellate cell (HSC) activation and subsequent development of liver fibrosis via multiple mechanisms. Phosphatase and tensin homolog deletion 10 (PTEN) plays a crucial role in suppression of HSC activation, but its regulation by adiponectin is not fully understood. Here, we investigated the effect of adiponectin on PTEN in LX-2 cells, a human cell line and examined the underlying molecular mechanisms involved in adiponectin-mediated upregulation of PTEN activity during fibrosis. PTEN expression was found to be significantly reduced in the livers of mice treated with CCl4, whereas its expression was rescued by adiponectin treatment. The DNA methylation proteins DNMT1, DNMT3A, and DNMT3B are all highly expressed in activated primary HSCs compared to quiescent HSCs, and thus represent additional regulatory targets during liver fibrogenesis. Expression of DNMT proteins was significantly induced in the presence of fibrotic stimuli; however, only DNMT3B expression was reduced in the presence of adiponectin. Adiponectin-induced suppression of DNMT3B was found to be mediated by enhanced miR-29b expression. Furthermore, PTEN expression was significantly increased by overexpression of miR-29b, whereas its expression was markedly reduced by a miR-29b inhibitor in LX-2 cells. These findings suggest that adiponectin-induced upregulation of miR-29b can suppress DNMT3B transcription in LX-2 cells, thus resulting in reduced methylation of PTEN CpG islands and ultimately suppressing the PI3K/AKT pathway. Together, these data suggest a possible new explanation for the inhibitory effect of adiponectin on HSC activation and liver fibrogenesis.

show abstract

“…For instance, RNAi mediated knock-down of Dnmt3a, a DNA methyltransferase, had no effect on the in vitro phenotype of B16 cells but increased the expression of genes associated with MHC class I antigen processing and presentation and dramatically reduced tumor growth in vivo (Deng et al, 2009). Expression of Dnmt3a has been linked to epithelial-mesenchymal transition (EMT), where miRNAs that regulate Dnmt3a expression are lost upon EMT and enable de novo methylation to increase (Cicchini et al, 2015). In turn, EMT is induced by hypoxia (Cooke et al, 2012), which can become more prevalent within the tumor microenvironment as tumors increase in size.…”

Section: Discussionmentioning

confidence: 99%

Inferring the Impact of Regulatory Mechanisms that Underpin CD8+ T Cell Control of B16 Tumor Growth In vivo Using Mechanistic Models and Simulation

Klinke

Wang

2017

Front. Pharmacol.

View full text Add to dashboard Cite

A major barrier for broadening the efficacy of immunotherapies for cancer is identifying key mechanisms that limit the efficacy of tumor infiltrating lymphocytes. Yet, identifying these mechanisms using human samples and mouse models for cancer remains a challenge. While interactions between cancer and the immune system are dynamic and non-linear, identifying the relative roles that biological components play in regulating anti-tumor immunity commonly relies on human intuition alone, which can be limited by cognitive biases. To assist natural intuition, modeling and simulation play an emerging role in identifying therapeutic mechanisms. To illustrate the approach, we developed a multi-scale mechanistic model to describe the control of tumor growth by a primary response of CD8+ T cells against defined tumor antigens using the B16 C57Bl/6 mouse model for malignant melanoma. The mechanistic model was calibrated to data obtained following adenovirus-based immunization and validated to data obtained following adoptive transfer of transgenic CD8+ T cells. More importantly, we use simulation to test whether the postulated network topology, that is the modeled biological components and their associated interactions, is sufficient to capture the observed anti-tumor immune response. Given the available data, the simulation results also provided a statistical basis for quantifying the relative importance of different mechanisms that underpin CD8+ T cell control of B16F10 growth. By identifying conditions where the postulated network topology is incomplete, we illustrate how this approach can be used as part of an iterative design-build-test cycle to expand the predictive power of the model.

show abstract

Epigenetic control of EMT/MET dynamics: HNF4α impacts DNMT3s through miRs-29

Abstract: HNF4α maintains hepatocyte identity by regulating miR-29a and -29b expression, which in turn control epigenetic modifications by limiting DNMT3A and DNMT3B levels.

Cited by 63 publications

References 34 publications

Cocaine Self-administration Alters Transcriptome-wide Responses in the Brain’s Reward Circuitry

Cocaine Self-administration Alters Transcriptome-wide Responses in the Brain’s Reward Circuitry

Adiponectin inhibits hepatic stellate cell activation by targeting the PTEN/AKT pathway

Inferring the Impact of Regulatory Mechanisms that Underpin CD8+ T Cell Control of B16 Tumor Growth In vivo Using Mechanistic Models and Simulation

Contact Info

Product

Resources

About