DNA oxidation drives Myc mediated transcription

Amente, Stefano; Lania, Luigi; Avvedimento, Enrico V.; Majello, Barbara

doi:10.4161/cc.9.15.12499

Cited by 34 publications

(28 citation statements)

References 19 publications

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“…It has been reported that LSD1-mediated demethylation of H3K4 leads to the assembly of the c-Myc-induced transcription initiation complex (22,23). Therefore, we supposed that a complex containing c-Myc, HBXIP, LSD1, and others might be involved in the event.…”

Section: Discussionmentioning

confidence: 95%

“…It has been reported that LSD1-mediated demethylation of H3K4 acts as a driving force in the assembly of the c-Myc-induced transcription initiation complex (22,23); however, the mechanism remains unclear. Real-time PCR assays showed that the mRNA levels of LSD1 in the breast cancer cell lines were higher than those in the immortalized breast cell HBL-100 ( Supplementary Fig.…”

Section: Hbxip Serves As a Linker Of C-myc And Lsd1 In The Complex Ofmentioning

confidence: 99%

“…Lysine-specific demethylase 1 (LSD1)-mediated demethylation of H3K4 leads to local DNA oxidation as a driving force in the assembly of the c-Myc-induced transcription initiation complex (22,23). The epigenetics is involved in the c-Myc-mediated transcription (24,25).…”

Section: Introductionmentioning

confidence: 99%

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HBXIP and LSD1 Scaffolded by lncRNA Hotair Mediate Transcriptional Activation by c-Myc

et al. 2016

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c-Myc is regarded as a transcription factor, but the basis for its function remains unclear. Here, we define a long noncoding RNA (lncRNA)/protein complex that mediates the transcriptional activation by c-Myc in breast cancer cells. Among 388 c-Myc target genes in human MCF-7 breast cancer cells, we found that their promoters could be occupied by the oncoprotein HBXIP. We confirmed that the HBXIP expression correlated with expression of the c-Myc target genes cyclin A, eIF4E, and LDHA. RNAi-mediated silencing of HBXIP abolished c-Mycmediated upregulation of these target genes. Mechanistically, HBXIP interacted directly with c-Myc through the leucine zippers and recruited the lncRNA Hotair along with the histone demethylase LSD1, for which Hotair serves as a scaffold. Silencing of HBXIP, Hotair, or LSD1 was sufficient to block c-Myc-enhanced cancer cell growth in vitro and in vivo. Taken together, our results support a model in which the HBXIP/ Hotair/LSD1 complex serves as a critical effector of c-Myc in activating transcription of its target genes, illuminating longstanding questions on how c-Myc drives carcinogenesis. Cancer Res; 76(2); 293-304. Ó2015 AACR.

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Section: Discussionmentioning

confidence: 95%

Section: Hbxip Serves As a Linker Of C-myc And Lsd1 In The Complex Ofmentioning

confidence: 99%

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HBXIP and LSD1 Scaffolded by lncRNA Hotair Mediate Transcriptional Activation by c-Myc

et al. 2016

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“…More recently, the same group observed LSD1-BERmediated transcriptional regulation in Myc-activated transcription of the Myc-target genes Ncl and CAD (4,5). Myc is one of the most common activators of cell proliferation used by cancer cells to drive disease progression.…”

Section: Ber and Myc-induced Epigenetic Regulationmentioning

confidence: 99%

“…As we discussed above, defects in BER directly reduced estrogen-or Myc-induced target gene expression. The 8-oxodG lesion, produced from H 2 O 2 , generated by LSD1 or LSD2 during the process of histone demethylation, serves as the signal to recruit BER enzymes to hydrolyze and relax high GC-content promoter regions, facilitating and enhancing transcription initiation and elongation (5). Appropriately controlled epigenetic regulation is critical for the normal development and health of an organism.…”

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confidence: 99%

Base Excision Repair Facilitates a Functional Relationship Between Guanine Oxidation and Histone Demethylation

Braganza

Sobol

2013

Antioxidants & Redox Signaling

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Significance: Appropriately controlled epigenetic regulation is critical for the normal development and health of an organism. Misregulation of epigenetic control via deoxyribonucleic acid (DNA) methylation or histone methylation has been associated with cancer and chromosomal instability syndromes. Recent Advances: The main function of the proteins in the base excision repair (BER) pathway is to repair DNA single-strand breaks and deamination, oxidation, and alkylation-induced DNA base damage that may result from chemotherapy, environmental exposure, or byproducts of cellular metabolism. Recent studies have suggested that one or more BER proteins may also participate in epigenetic regulation to facilitate gene expression modulation via alteration of the state of DNA methylation or via a reaction coupled to histone modification. BER proteins have also been reported to play an essential role in pluripotent stem cell reprogramming. Critical Issues: One emerging function for BER in epigenetic regulation is the repair of base lesions induced by hydrogen peroxide as a byproduct of lysine-specific demethylase 1 (LSD1) enzymatic activity (LSD1/LSD2-coupled BER) for transcriptional regulation. Future Directions: To shed light on this novel role of BER, this review focuses on the repair of oxidative lesions in nuclear DNA that are induced during LSD1-mediated histone demethylation. Further, we highlight current studies suggesting a role for BER proteins in transcriptional regulation of gene expression via BERcoupled active DNA demethylation in mammalian cells. Such efforts to address the role of BER proteins in epigenetic regulation could broaden cancer therapeutic strategies to include epigenetic modifiers combined with BER inhibitors.

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8‐Oxo‐7,8‐dihydroguanine and uric acid as efficient predictors of survival in colon cancer patients

Dziaman

Banaszkiewicz

Roszkowski

et al. 2013

Intl Journal of Cancer

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The aim of this work was to answer the question whether the broad range of parameters which describe oxidative stress and oxidatively damaged DNA and repair are appropriate prognosis factors of colon cancer (CRC) patients survival? The following parameters were analyzed for 89 CRC patients: concentration of uric acid and vitamins A, E, C in plasma; levels of 8-oxodGuo (8-oxo-7,8-dihydro-2 0 -deoxyguanosine) in DNA of leukocyte and colon tissues; urinary excretion rates of 8-oxodGuo and 8-oxoGua (8-oxo-7,8-dihydroguanine); the activity and mRNA or protein level of repair enzymes OGG1, APE1, ANPG, TDG and PARP1. All DNA modifications and plasma antioxidants were analyzed using high performance liquid chromatography (HPLC) or HPLC/gas chromatography-mass spectrometry techniques. Expression of repair proteins was analyzed by QPCR, Western or immunohistochemistry methods. Longer survival coincided with low levels of 8-oxodGuo/8oxoGua in urine and 8-oxodGuo in DNA as well as with high concentration of uric acid plasma level. In contrast to expectations, longer survival coincided with lower mRNA level in normal colon tissue of the main 8-oxoGua DNA glycosylase, OGG1, but no association was found for PARP-1 expression. When analyzing simultaneously two parameters the discriminating power increased significantly. Combination of low level of urinary 8-oxoGua together with low level of 8-oxodGuo in leukocyte (both below median value) or high concentration of plasma uric acid (above median value) have the best prediction power. Since prediction value of these parameters seems to be comparable to conventional staging procedure, they could possibly be used as markers to predict clinical success in CRC treatment.

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DNA oxidation drives Myc mediated transcription

Cited by 34 publications

References 19 publications

HBXIP and LSD1 Scaffolded by lncRNA Hotair Mediate Transcriptional Activation by c-Myc

HBXIP and LSD1 Scaffolded by lncRNA Hotair Mediate Transcriptional Activation by c-Myc

Base Excision Repair Facilitates a Functional Relationship Between Guanine Oxidation and Histone Demethylation

8‐Oxo‐7,8‐dihydroguanine and uric acid as efficient predictors of survival in colon cancer patients

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