BTG2: A rising star of tumor suppressors (Review)

Mao, Bijing; Zhang, Zhimin; Wang, Ge

doi:10.3892/ijo.2014.2765

Cited by 121 publications

(111 citation statements)

References 56 publications

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“…Metastasis Suppressor 1 ( MTSS1 ), is inactivated in metastatic cancer [39] and has prognostic value for breast cancer [40] and lung cancer [41]. NKX6-2 and BTG2 (B-Cell Translocation Gene 2) are candidate tumor suppressor genes [42,43]. Further analysis of MTSS1 , NKX6-2 , and BTG2 in the blood of heavy, long-time smokers might reveal a relationship between methylation and early signs of pathology or disease.…”

Section: Discussionmentioning

confidence: 99%

Distinct Epigenetic Effects of Tobacco Smoking in Whole Blood and among Leukocyte Subtypes

Su¹,

Wang²,

Campbell³

et al. 2016

PLoS ONE

111

124

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Tobacco smoke exposure dramatically alters DNA methylation in blood cells and may mediate smoking-associated complex diseases through effects on immune cell function. However, knowledge of smoking effects in specific leukocyte subtypes is limited. To better characterize smoking–associated methylation changes in whole blood and leukocyte subtypes, we used Illumina 450K arrays and Reduced Representation Bisulfite Sequencing (RRBS) to assess genome-wide DNA methylation. Differential methylation analysis in whole blood DNA from 172 smokers and 81 nonsmokers revealed 738 CpGs, including 616 previously unreported CpGs, genome-wide significantly associated with current smoking (p <1.2x10-7, Bonferroni correction). Several CpGs (MTSS1, NKX6-2, BTG2) were associated with smoking duration among heavy smokers (>22 cigarettes/day, n = 86) which might relate to long-term heavy-smoking pathology. In purified leukocyte subtypes from an independent group of 20 smokers and 14 nonsmokers we further examined methylation and gene expression for selected genes among CD14+ monocytes, CD15+ granulocytes, CD19+ B cells, and CD2+ T cells. In 10 smokers and 10 nonsmokers we used RRBS to fine map differential methylation in CD4+ T cells, CD8+ T cells, CD14+, CD15+, CD19+, and CD56+ natural killer cells. Distinct cell-type differences in smoking-associated methylation and gene expression were identified. AHRR (cg05575921), ALPPL2 (cg21566642), GFI1 (cg09935388), IER3 (cg06126421) and F2RL3 (cg03636183) showed a distinct pattern of significant smoking-associated methylation differences across cell types: granulocytes> monocytes>> B cells. In contrast GPR15 (cg19859270) was highly significant in T and B cells and ITGAL (cg09099830) significant only in T cells. Numerous other CpGs displayed distinctive cell-type responses to tobacco smoke exposure that were not apparent in whole blood DNA. Assessing the overlap between these CpG sites and differential methylated regions (DMRs) with RRBS in 6 cell types, we confirmed cell-type specificity in the context of DMRs. We identified new CpGs associated with current smoking, pack-years, duration, and revealed unique profiles of smoking-associated DNA methylation and gene expression among immune cell types, providing potential clues to hematopoietic lineage-specific effects in disease etiology.

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Section: Discussionmentioning

confidence: 99%

Distinct Epigenetic Effects of Tobacco Smoking in Whole Blood and among Leukocyte Subtypes

Su¹,

Wang²,

Campbell³

et al. 2016

PLoS ONE

111

124

View full text Add to dashboard Cite

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“…Tbx20 also directly binds to and represses cell-cycle inibitory genes p21 and Meis1 , and a novel anti-proliferative protein gene Btg2, concomitant with inducing CM proliferation. The anti-proliferative effects of Btg2 in tumor cells has made it a promising target for cancer treatment 28 , but its role in regulating CM proliferation downstream of Tbx20 and potential effects on CM regeneration have not previously been reported. These findings demonstrate that proliferation of differentiated adult CM can be induced by overexpression of a single transcription factor without compromising heart structure or function and that these hearts have improved cardiac performance and survival post-MI.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Tbx20 in Adult Cardiomyocytes Promotes Proliferation and Improves Cardiac Function After Myocardial Infarction

2016

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Background Adult mammalian cardiomyocytes (CM) have the potential to proliferate, but this is not sufficient to generate adequate CMs after myocardial infarction (MI). The transcription factor Tbx20 is required for CM proliferation during development and adult CM homeostasis. The ability of Tbx20 overexpression (Tbx20OE) to promote adult CM proliferation and improve cardiac function after MI was examined. Methods and Results Tbx20OE was induced specifically in adult mouse differentiated CMs. Increased CM proliferation and fetal-like characteristics were found in Tbx20OE hearts, compared to controls, without causing pathology 4 weeks after Tbx20OE at baseline. Moreover, Tbx20OE in adult CM after MI significantly improved survival, cardiac function, and infarct size 4 weeks post-MI. Improved cardiac repair, as indicated by increased CM proliferation and capillary density, was observed in the MI border zone of Tbx20OE hearts compared to controls. Expression of proliferation activator (cyclin D1, E1, and IGF1) and fetal contractile protein (ssTNI, βMHC) mRNA was increased, while negative cell-cycle regulators (p21, Meis1) were decreased, in Tbx20OE hearts, compared to controls, under both baseline and MI conditions. Tbx20OE in adult hearts activates multiple pro-proliferation pathways including Akt, YAP and BMP. Interestingly, p21, Meis1, and a novel cell-cycle inhibitory gene Btg2, are directly bound and repressed by Tbx20 with induction of proliferation in neonatal CM. Conclusions Tbx20OE specifically in adult CM activates multiple cardiac proliferative pathways, directly represses cell-cycle inhibitory genes p21, Meis1 and Btg2, promotes adult CM proliferation, and preserves cardiac performance post-MI.

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“…BTG2 encodes for a member of the BTG/Tob family, which includes structurally related proteins that appear to have antiproliferative properties. BTG2 is involved in the regulation of the G1/S transition of the cell cycle (Mao et al, 2015) and DNA damage repair (Rouault et al, 1996). This may imply that NannoG treatment provides the cell with the ability, upon stress, to activate cytoprotective processes like cell cycle arrest and DNA repair.…”

Section: Nannog Positively Regulated Genes Involves In Skin Texture Amentioning

confidence: 99%

Skin Protective Effects of Nannochloropsis gaditana Extract on H2O2-Stressed Human Dermal Fibroblasts

Letsiou¹,

Kalliampakou

Gardikis³

et al. 2017

Front. Mar. Sci.

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Nowadays, there is huge interest in natural products obtained from marine organisms that can promote a state of health and well-being for humans. Microalgae represent a primary source of bioactive compounds that could be used as functional ingredients in cosmetic formulations. The aim of the present study is to evaluate, for the first time, the effects of Nannochloropsis gaditana extract against oxidative stress in human primary fibroblasts so as to investigate the potential applications of it in cosmetics. To gain an insight into the molecular mechanisms of N. gaditana bioactivity, we developed a new RT-qPCR platform for studying transcript accumulation for an array of selected genes (up to 100) involved in many skin-related processes including anti-aging, hydration, oxidative stress response, and DNA damage. For the oxidative stress evaluation, H 2 O 2 was used as a stressor. The study of the transcript accumulation of genes revealed that N. gaditana extract exhibits skin protection properties by mediating oxidative responses and apoptosis (including SOD1, GPX1, BID), positively regulates genes involves in skin texture and hydration (including AQP3, Col6A1, FBN1) and modulates the expression of genes involved in skin irritation, DNA damage and aging (including IL1R, PCNA, FOXO3). These findings indicate that the specific N. gaditana extract possesses significant in vitro skin protection activity against induced oxidative stress, and provide new insights into the beneficial role of microalgae bioactive compounds in cosmetic formulations protecting skin from oxidative stress.

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BTG2: A rising star of tumor suppressors (Review)

Cited by 121 publications

References 56 publications

Distinct Epigenetic Effects of Tobacco Smoking in Whole Blood and among Leukocyte Subtypes

Distinct Epigenetic Effects of Tobacco Smoking in Whole Blood and among Leukocyte Subtypes

Overexpression of Tbx20 in Adult Cardiomyocytes Promotes Proliferation and Improves Cardiac Function After Myocardial Infarction

Skin Protective Effects of Nannochloropsis gaditana Extract on H2O2-Stressed Human Dermal Fibroblasts

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