MYC—Master Regulator of the Cancer Epigenome and Transcriptome

Poole, Candace J.; Riggelen, Jan van

doi:10.3390/genes8050142

Cited by 140 publications

(119 citation statements)

References 192 publications

(268 reference statements)

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“…Koga et al, () demonstrated that miR‐302 induces H3K4 methylation through downregulation of AOF2, resulting in MYC repression, apoptosis, and drug sensitivity in hepatocellular carcinoma cells. Considering the oncogenic function of MYC and its pivotal role as a master regulator of the cancer epigenome and transcriptome (Poole & van Riggelen, ), downregulation of MYC by miR‐302 cluster may explain some of the anti‐tumor effects of miR‐302 cluster we observed in breast cancer cells. Sustaining proliferative signaling is one of the fundamental features of cancer development (Hanahan & Weinberg, ).…”

Section: Discussionmentioning

confidence: 90%

Vitamin C counteracts miR‐302/367‐induced reprogramming of human breast cancer cells and restores their invasive and proliferative capacity

Ramezankhani

Taha

Javeri

2018

Journal Cellular Physiology

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Epigenetic reprogramming by embryonic stem cell-specific miR-302/367 cluster has shown some tumor suppressive effects in cancer cells of different tissues such as skin, colon, and cervix. Vitamin C has been known as a reprogramming enhancer of human and mouse somatic cells. In this study, first we aimed to investigate whether exogenous induction of miR-302/367 in breast cancer cells shows the same tumor suppressive effects previously observed in other cancer cells lines, and whether vitamin C can enhance reprogramming of breast cancer cells and also improve the tumor suppressive function of miR-302/367 cluster. Overexpression of miR-302/367 cluster in MDA-MB-231 and SK-BR-3 breast cancer cells upregulated expression of miR-302/367 members and also some core pluripotency factors including OCT4A, SOX2 and NANOG, induced mesenchymal to epithelial transition, suppressed invasion, proliferation, and induced apoptosis in the both cell lines. However, treatment of the miR-302/367 transfected cells with vitamin C suppressed the expression of pluripotency factors and augmented the tumorigenicity of the breast cancer cells by restoring their proliferative and invasive capacity and compromising the apoptotic effect of miR-302/367. Supplementing the culture medium with vitamin C downregulated expression of TET1 gene which seems to be the reason behind the negative impact of vitamin C on the reprogramming efficiency of miR-302/367 cluster and its anti-tumor effects. Therefore application of vitamin C may not always serve as a reprogramming enhancer depending on its switching function on TET1. This phenomenon should be carefully considered when considering a reprogramming strategy for tumor suppression.

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Section: Discussionmentioning

confidence: 90%

Vitamin C counteracts miR‐302/367‐induced reprogramming of human breast cancer cells and restores their invasive and proliferative capacity

Ramezankhani

Taha

Javeri

2018

Journal Cellular Physiology

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“…[17,27,28] The sheer number and variety of MYC targets has sparked intense interest in both regulatory mechanisms and function. Detailed analysis of MYC function have been reviewed comprehensively elsewhere, [29][30][31] and although a complete discussion is beyond the scope of this review, we provide some brief background. MYC is a member of the basic helix-loop-helix (bHLH) protein family, which heterodimerizes with its binding partner MAX to stimulate transcription.…”

Section: Introductionmentioning

confidence: 99%

DNA Conformation Regulates Gene Expression: The MYC Promoter and Beyond

Zaytseva

Quinn

2018

BioEssays

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Emerging evidence suggests that DNA topology plays an instructive role in cell fate control through regulation of gene expression. Transcription produces torsional stress, and the resultant supercoiling of the DNA molecule generates an array of secondary structures. In turn, local DNA architecture is harnessed by the cell, acting within sensory feedback mechanisms to mediate transcriptional output. MYC is a potent oncogene, which is upregulated in the majority of cancers; thus numerous studies have focused on detailed understanding of its regulation. Dissection of regulatory regions within the MYC promoter provided the first hint that intimate feedback between DNA topology and associated DNA remodeling proteins is critical for moderating transcription. As evidence of such regulation is also found in the context of many other genes, here we expand on the prototypical example of the MYC promoter, and also explore DNA architecture in a genome-wide context as a global mechanism of transcriptional control.

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“…The oncogenic protein c-Myc, which is constitutively expressed in a variety of aggressive tumors, including glioblastomas, acts not only as a transcription factor, but as a global regulator of pro-tumor epigenetic modifications (57). We found that c-Myc expression in U87 cells underwent a rapid decline after PDT, beginning immediately after irradiation, reaching a nadir at ~3 h, and then gradually rising so that the c-Myc level at 24 h approximated that of the nonirradiated control (Fig.…”

Section: Jq1-inhibitable Induction Of Other Prosurvival/pro-invasion mentioning

confidence: 99%

Nitric oxide antagonism to glioblastoma photodynamic therapy and mitigation thereof by BET bromodomain inhibitor JQ1

Fahey

Stancill

Smith

et al. 2018

Journal of Biological Chemistry

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Endogenous nitric oxide (NO) generated by inducible NO synthase (iNOS) promotes glioblastoma cell proliferation and invasion, and also plays a key role in glioblastoma resistance to chemotherapy and radiotherapy. Non-ionizing photodynamic therapy (PDT) has anti-tumor advantages over conventional glioblastoma therapies. Our previous studies revealed that glioblastoma U87 cells upregulate iNOS after a photodynamic challenge and that resulting NO not only increased resistance to apoptosis, but rendered surviving cells more proliferative and invasive. These findings were largely based on the effects of inhibiting iNOS activity and scavenging NO. Demonstrating now that iNOS expression in photostressed U87 cells is mediated by NF-κB, we hypothesized that (i) recognition of acetylated lysine (acK) on NF-κB p65/Rel A by bromodomain and extra-terminal (BET) protein Brd4 is crucial, and (ii) by suppressing iNOS expression, a BET inhibitor (JQ1) would attenuate the negative effects of photostress. The following evidence was obtained: (i) Like iNOS, Brd4 protein and p65-acK levels increased several fold in photostressed cells; (ii) JQ1 at minimally toxic concentrations had no effect on Brd4 or p65-acK upregulation after PDT, but strongly suppressed iNOS, survivin, and Bcl-xL upregulation, along with the growth and invasion spurt of PDTsurviving cells; (iii) JQ1 inhibition of NO production in photostressed cells closely paralleled that of growth/invasion inhibition; (iv) At 1% the concentration of iNOS inhibitor 1400W, JQ1 reduced post-PDT cell aggressiveness to a far greater extent. This is the first evidence for BET inhibitor targeting of iNOS expression in cancer cells and how such targeting can markedly improve therapeutic efficacy.

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MYC—Master Regulator of the Cancer Epigenome and Transcriptome

Cited by 140 publications

References 192 publications

Vitamin C counteracts miR‐302/367‐induced reprogramming of human breast cancer cells and restores their invasive and proliferative capacity

Vitamin C counteracts miR‐302/367‐induced reprogramming of human breast cancer cells and restores their invasive and proliferative capacity

DNA Conformation Regulates Gene Expression: The MYC Promoter and Beyond

Nitric oxide antagonism to glioblastoma photodynamic therapy and mitigation thereof by BET bromodomain inhibitor JQ1

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