Effects of deranged metabolism on epigenetic changes in cancer

Chandra, Vishal; Hong, Kyeong-Man

doi:10.1007/s12272-015-0561-3

Cited by 10 publications

(9 citation statements)

References 200 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4d and e ) and activation of additional adaptive pathways related to gene expression regulation (alternative splicing and post-transcriptional modifications). Importantly, many DEPs were associated with metabolic processes involved in histone modification and chromatin organization (Additional file 1 : Table S4), that could contribute to heritable epigenetic changes via chromatin remodeling [ 44 ]. It was proposed that DNA damage give rise to mRNA splicing by post-translational modification of splicing factor [ 45 ] and alternative splicing of the components of the two critical pathways in PCa, AR and PI3K, was involved both in cancer development and in therapy escape [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Adaptive phenotype drives resistance to androgen deprivation therapy in prostate cancer

et al. 2017

View full text Add to dashboard Cite

BackgroundProstate cancer (PCa), the second most common cancer affecting men worldwide, shows a broad spectrum of biological and clinical behaviour representing the epiphenomenon of an extreme heterogeneity. Androgen deprivation therapy is the mainstay of treatment for advanced forms but after few years the majority of patients progress to castration-resistant prostate cancer (CRPC), a lethal form that poses considerable therapeutic challenges.MethodsWestern blotting, immunocytochemistry, invasion and reporter assays, and in vivo studies were performed to characterize androgen resistant sublines phenotype in comparison to the parental cell line LNCaP. RNA microarray, mass spectrometry, integrative transcriptomic and proteomic differential analysis coupled with GeneOntology and multivariate analyses were applied to identify deregulated genes and proteins involved in CRPC evolution.ResultsTreating the androgen-responsive LNCaP cell line for over a year with 10 μM bicalutamide both in the presence and absence of 0.1 nM 5-α-dihydrotestosterone (DHT) we obtained two cell sublines, designated PDB and MDB respectively, presenting several analogies with CRPC. Molecular and functional analyses of PDB and MDB, compared to the parental cell line, showed that both resistant cell lines were PSA low/negative with comparable levels of nuclear androgen receptor devoid of activity due to altered phosphorylation; cell growth and survival were dependent on AKT and p38MAPK activation and PARP-1 overexpression; their malignant phenotype increased both in vitro and in vivo. Performing bioinformatic analyses we highlighted biological processes related to environmental and stress adaptation supporting cell survival and growth. We identified 15 proteins that could direct androgen-resistance acquisition. Eleven out of these 15 proteins were closely related to biological processes involved in PCa progression.ConclusionsOur models suggest that environmental factors and epigenetic modulation can activate processes of phenotypic adaptation driving drug-resistance. The identified key proteins of these adaptive phenotypes could be eligible targets for innovative therapies as well as molecules of prognostic and predictive value.Electronic supplementary materialThe online version of this article (10.1186/s12964-017-0206-x) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Adaptive phenotype drives resistance to androgen deprivation therapy in prostate cancer

et al. 2017

View full text Add to dashboard Cite

show abstract

“…There is also a report of varied epithelial gene and protein expression patterns along the human and mouse small intestines, with bicarbonate transporters prominent in the duodenum, where acidic stomach contents are neutralised, digestive enzymes and nutrient transporters highly expressed in the jejunum, and bile acid transporters present in the ileum 15 . However, Wright and Alison 11 state that rodent small intestine does not show a distinct duodenum, jejunum and ileum, which could explain our observations of linear metabolic gradients rather than three discontinuous concentrations. Indeed, it has been known for many years that there are continuous anatomical gradients along the mouse small intestine 16 .…”

Section: Discussionmentioning

confidence: 60%

“…Thus the increased mean concentration levels of t-Cho, glycine, glutamate, leucine and t-Cr in Apc Min/+ mouse tumours compared to NAdj samples are consistent with metabolic reprogramming of phospholipid, amino acid and energy metabolism in the tumour tissue. Cancer cell metabolism is also associated with epigenetic changes 11 . The Warburg effect can affect histone acetylation and cell proliferation through mechanisms mediated by butyrate 22 and hydroxybutyrate 23 , whereas other metabolites including S-adenosyl methionine and 2-hydroxyglutarate are required for DNA methyltransferase (Dnmt) and hydroxylase activity 24 .…”

Section: Discussionmentioning

confidence: 99%

“…HR-MAS 1 H NMR is less sensitive than mass spectrometry (hence the limited number of metabolites analysed herein) but it has the advantage that metabolites are assayed in the original sample, with no errors due to extraction, derivatisation or ionisation; also, the sample is unaffected by the spectroscopic procedure, so the metabolite data can be paired to data from additional analyses. Because epigenetic changes associate with gene activity 8 , cellular proliferation 9,10 and cancer cell metabolism 11 we measured cytosine methylation and hydroxymethylation in DNA extracted from the tissue biopsies that had been used for the metabolite analysis.…”

mentioning

confidence: 99%

See 1 more Smart Citation

ApcMin/+ tumours and normal mouse small intestines show linear metabolite concentration and DNA cytosine hydroxymethylation gradients from pylorus to colon

Madhu

Uribe-Lewis

Bachman

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Topographical variations of metabolite concentrations have been reported in the duodenum, jejunum and ileum of the small intestine, and in human intestinal tumours from those regions, but there are no published metabolite concentrations measurements correlated with linear position in the mouse small intestine or intestinal tumours. Since DNA methylation dynamics are influenced by metabolite concentrations, they too could show linear anatomical variation. We measured metabolites by HR-MAS 1 H NMR spectroscopy and DNA cytosine modifications by LC/MS, in normal small intestines of C57BL/6J wild-type mice, and in normal and tumour samples from Apc Min/+ mice. Wild-type mouse intestines showed approximately linear, negative concentration gradations from the pylorus (i.e. the junction with the stomach) of alanine, choline compounds, creatine, leucine and valine. Apc Min/+ mouse tumours showed negative choline and valine gradients, but a positive glycine gradient. 5-Hydroxymethylcytosine showed a positive gradient in the tumours. The linear gradients we found along the length of the mouse small intestine and in tumours contrast with previous reports of discrete concentration changes in the duodenum, jejunum and ileum. To our knowledge, this is also the first report of a systematic measurement of global levels of DNA cytosine modification in wild-type and Apc Min/+ mouse small intestine.

show abstract

“…Mutations in these epigenetic regulatory genes are essential for tumor formation . DNA methyltransferase and histone‐modifying enzymes are frequently mutated in malignant tumor cells, and epigenetic changes appear important for maintaining tumor formation . Therefore, the editing of the epigenome shows the importance of correcting tumor epigenetic disorders at the gene level.…”

Section: Using Crispr/cas9 In the Study Of Tumor Therapiesmentioning

confidence: 99%

Application of CRISPR/Cas9 gene editing technique in the study of cancer treatment

et al. 2019

View full text Add to dashboard Cite

In recent years, gene editing, especially that using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9, has made great progress in the field of gene function. Rapid development of gene editing techniques has contributed to their significance in the field of medicine. Because the CRISPR/Cas9 gene editing tool is not only powerful but also has features such as strong specificity and high efficiency, itcan accurately and rapidly screen the whole genome, facilitating the administration of gene therapy for specific diseases. In the field of tumor research, CRISPR/Cas9 can be used to edit genomes to explore the mechanisms of tumor occurrence, development, and metastasis. In these years, this system has been increasingly applied in tumor treatment research. CRISPR/Cas9 can be used to treat tumors by repairing mutations or knocking out specific genes. To date, numerous preliminary studies have been conducted on tumor treatment in related fields. CRISPR/Cas9 holds great promise for gene-level tumor treatment. Personalized and targeted therapy based on CRISPR/Cas9 will possibly shape the development of tumor therapy in the future. In this study, we review the findings of CRISPR/Cas9 for tumor treatment research to provide references for related future studies on the pathogenesis and clinical treatment of tumors.

show abstract

Effects of deranged metabolism on epigenetic changes in cancer

Cited by 10 publications

References 200 publications

Adaptive phenotype drives resistance to androgen deprivation therapy in prostate cancer

Adaptive phenotype drives resistance to androgen deprivation therapy in prostate cancer

ApcMin/+ tumours and normal mouse small intestines show linear metabolite concentration and DNA cytosine hydroxymethylation gradients from pylorus to colon

Application of CRISPR/Cas9 gene editing technique in the study of cancer treatment

Contact Info

Product

Resources

About