Hydroxyurea promotes TET1 expression and induces apoptosis in osteosarcoma cells

Teng, Songsong; Ma, Chunhui; Ye, Yu; Che, Yi

doi:10.1042/bsr20190456

Cited by 18 publications

(11 citation statements)

References 28 publications

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“…HU inactivates ribonucleotide reductase and inhibits DNA synthesis in proliferating cells, and can increase apoptosis and induce cell cycle changes [11,13,14]. Accordingly, HU exposure induced apoptosis of fetal tissue cells, which resulted in abnormal tissue development in offspring [15]. HU can increase the production of reactive oxygen species (ROS) [8,16].…”

Section: Introductionmentioning

confidence: 99%

Hydroxyurea affects in vitro porcine oocyte maturation through increased apoptosis and oxidative stress

et al. 2021

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Hydroxyurea (HU) is an FDA-approved drug used to treat a variety of diseases, especially malignancies, but is harmful to fertility. We used porcine oocytes as an experimental model to study the effect of HU during oocyte maturation. Exposure of cumulus-oocyte complexes (COCs) to 20 µM (p < 0.01) and 50 µM (p < 0.001) HU reduced oocyte maturation. Exposure to 20 µM HU induced approximately 1.5-fold and 2-fold increases in Caspase-3 (p < 0.001) and P53 (p < 0.01) gene expression levels in cumulus cells, respectively, increased Caspase-3 (p < 0.01) and P53 (p < 0.001) protein expression levels in metaphase II (MII) oocytes and increased the percentage of apoptotic cumulus cells (p < 0.001). In addition, HU decreased the mitochondrial membrane potential (Δφm) (p < 0.01 and p < 0.001) and glutathione (GSH) levels (p < 0.01 and p < 0.001) of both cumulus cells and MII oocytes, while increasing their reactive oxygen species (ROS) levels (p < 0.001). Following parthenogenetic activation of embryos derived from MII oocytes, exposure to 20 µM HU significantly reduced total blastocyst cell numbers (p < 0.001) and increased apoptosis of blastocyst cells (p < 0.001). Moreover, HU exposure reduced the rate of development of 2-cell, 4 -8 cell, blastocyst, and hatching stages after parthenogenetic activation (p < 0.05). Our findings indicate that exposure to 20 µM HU caused significant oxidative stress and apoptosis of MII oocytes during maturation, which affected their developmental ability. These results provide valuable information for safety assessments of HU.

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Section: Introductionmentioning

confidence: 99%

Hydroxyurea affects in vitro porcine oocyte maturation through increased apoptosis and oxidative stress

et al. 2021

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“…In this regard, we interacted our newly identified m 6 A methylated mRNAs and apoptosis related genes in the GeneCards and three of them were correlated to apoptosis (e.g., Tet1, Hadh, and Kcnn1). Over-expression of Tet1 increased cell apoptosis and inhibited cell growth in osteosarcoma cells (Teng et al, 2019). Over-expression of Hadh linked to cell apoptosis in acute myeloid leukemia (Wei L. et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Validated Impacts of N6-Methyladenosine Methylated mRNAs on Apoptosis and Angiogenesis in Myocardial Infarction Based on MeRIP-Seq Analysis

Zhang

Hua

Dang

et al. 2022

Front. Mol. Biosci.

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Objectives: N6-methyladenosine (m6A) is hypothesized to play a role in the regulation of pathogenesis of myocardial infarction (MI). This study was designed to compare m6A-tagged transcript profiles to identify mRNA-specific changes on pathophysiological variations after MI.Methods: N6-methyladenosine methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were interacted to select m6A-modified mRNAs with samples collected from sham operated and MI rat models. m6A methylation regulated mRNAs were interacted with apoptosis/angiogenesis related genes in GeneCards. Afterwards, MeRIP-quantitative real-time PCR (MeRIP-qRT-PCR) was performed to measure m6A methylation level of hub mRNAs. m6A methylation variation was tested under different oxygen concentration or hypoxic duration in H9c2 cells and HUVECs. In addition, Western blot and qRT-PCR were employed to detect expression of hub mRNAs and relevant protein level. Flow cytometry and Tunel assay were conducted to assess apoptotic level. CCK-8, EdU, and tube formation assay were performed to measure cell proliferation and tube formation ability.Results: Upregulation of Mettl3 was firstly observed in vivo and in vitro, followed by upregulation of m6A methylation level. A total of 567 significantly changed m6A methylation peaks were identified, including 276 upregulated and 291 downregulated peaks. A total of 576 mRNAs were upregulated and 78 were downregulated. According to combined analysis of MeRIP-seq and RNA-seq, we identified 26 significantly hypermethylated and downregulated mRNAs. Based on qRT-PCR and interactive analysis, Hadh, Kcnn1, and Tet1 were preliminarily identified as hub mRNAs associated with apoptosis/angiogenesis. MeRIP-qRT-PCR assay confirmed the results from MeRIP-seq. With the inhibition of Mettl3 in H9c2 cells and HUVECs, downregulated m6A methylation level of total RNA and upregulated expression of hub mRNAs were observed. Increased m6A level was verified in the gradient context in terms of prolonged hypoxic duration and decreased oxygen concentration. Under simulated hypoxia, roles of Kcnn1 and Tet1 in angiogenesis and Hadh, Tet1, and Kcnn1 in apoptosis were further confirmed with our validation experiments.Conclusion: Roles of m6A-modified mRNA transcripts in the context of MI were preliminarily verified. In the context of m6A methylation, three hub mRNAs were validated to impact the process of apoptosis/angiogenesis. Our study provided theoretical basis and innovative targets for treatment of MI and paved the way for future investigations aiming at exploring upstream epigenetic mechanisms of pathogenesis after MI.

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“…TET2 mutations affect non-CpG island DNA methylation at enhancers and transcription factor-binding sites in chronic myelomonocytic leukemia [69]. TET1 expression regulates proliferation and apoptosis in osteosarcoma cells [70]. Vitamin C promotes apoptosis in breast cancer cells by increasing TRAIL expression through TET-dependent DNA demethylation [71].…”

Section: Epigenetics Mechanisms Of Cancer Apoptosis Evasionmentioning

confidence: 99%

Epigenetic Deregulation of Apoptosis in Cancers

Ozyerli-Goknar

Bagcı-Önder

2021

Cancers

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Cancer cells possess the ability to evade apoptosis. Genetic alterations through mutations in key genes of the apoptotic signaling pathway represent a major adaptive mechanism of apoptosis evasion. In parallel, epigenetic changes via aberrant modifications of DNA and histones to regulate the expression of pro- and antiapoptotic signal mediators represent a major complementary mechanism in apoptosis regulation and therapy response. Most epigenetic changes are governed by the activity of chromatin modifying enzymes that add, remove, or recognize different marks on histones and DNA. Here, we discuss how apoptosis signaling components are deregulated at epigenetic levels, particularly focusing on the roles of chromatin-modifying enzymes in this process. We also review the advances in cancer therapies with epigenetic drugs such as DNMT, HMT, HDAC, and BET inhibitors, as well as their effects on apoptosis modulation in cancer cells. Rewiring the epigenome by drug interventions can provide therapeutic advantage for various cancers by reverting therapy resistance and leading cancer cells to undergo apoptotic cell death.

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Hydroxyurea promotes TET1 expression and induces apoptosis in osteosarcoma cells

Cited by 18 publications

References 28 publications

Hydroxyurea affects in vitro porcine oocyte maturation through increased apoptosis and oxidative stress

Hydroxyurea affects in vitro porcine oocyte maturation through increased apoptosis and oxidative stress

Validated Impacts of N6-Methyladenosine Methylated mRNAs on Apoptosis and Angiogenesis in Myocardial Infarction Based on MeRIP-Seq Analysis

Epigenetic Deregulation of Apoptosis in Cancers

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