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JMJD2B knockdown treatment in normoxia and hypoxia

ABSTRACT: Estrogen receptor alpha plays a critical role in breast cancer and is a major target in endocrine therapy. HIF-1 alpha have been associated with ER alpha and predict a worse outcome. Recent studies indicate that histone demethylase JMJD2B is a HIF-1 alpha target. However, little is known about the biological functions of JMJD2B, especially in breast cancer. To elucidate the mechanism by which JMJD2B reguates gene expression in normoxia and hypoxia, MCF-7 breast cancer cells were depleted forJMJD2B in normoxia and hypoxia. Our results provide insight into JMJD2B regulation of gene expression in breast cancer cells in normoxia and hypoxia. MCF7 cells were subjected to transfection with siRNA controls and two different siRNA oligos against JMJD2B for 24 hours. Cells were treated in normoxia and hypoxia for another 16 hours.

ORGANISM(S): Homo sapiens

SUBMITTER: Yang J

PROVIDER: S-ECPF-GEOD-18384 | biostudies-other | 2010 Aug

REPOSITORIES: biostudies-other

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JMJD2B knockdown treatment in normoxia and hypoxia

Project description:Estrogen receptor alpha plays a critical role in breast cancer and is a major target in endocrine therapy. HIF-1 alpha have been associated with ER alpha and predict a worse outcome. Recent studies indicate that histone demethylase JMJD2B is a HIF-1 alpha target. However, little is known about the biological functions of JMJD2B, especially in breast cancer. To elucidate the mechanism by which JMJD2B reguates gene expression in normoxia and hypoxia, MCF-7 breast cancer cells were depleted forJMJD2B in normoxia and hypoxia. Our results provide insight into JMJD2B regulation of gene expression in breast cancer cells in normoxia and hypoxia.

2010-09-01 | GSE18384 | GEO

JMJD2B knockdown treatment in normoxia and hypoxia

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Scrambled Control and EGFR Knockdown Cells Cultured under Normoxia and Hypoxia

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2013-10-01 | GSE44804 | GEO

Scrambled Control and EGFR Knockdown Cells Cultured under Normoxia and Hypoxia

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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mesendoderm differentiation with Hif-1a overexpression and knockdown under normoxia or hypoxia

Project description:To study the gene expression profile in the mesendoderm differerntiation of control and Hif-1a overexpression, we performed RNA-seq on the total RNA samples collected from the differentiation of control and Hif-1a overexpression AB2.2 mESCs at differentiation day 4.In addition, to study the gene expression profile in the mesendoderm differerntiation of Hif-1a knockdown under normoxia and hypoxia, we performed RNA-seq on the total RNA samples collected from the differentiation of Hif-1a knockdown AB2.2 mESCs under normoxia or hypoxia at differentiation day 4. Cell lines were built by infecting AB2.2 cells with lentiviruses. Each group contained three biological replicates. The expression matrix was obtained by Hisat2 followed by Stringtie.

2022-09-27 | GSE208062 | GEO

Normoxia versus hypoxia exposure

Project description:Exposure to 20.9% or 10.5% O2 for 24 hours of wildtype control mice, mice reloaded after hindlimb suspension and control HIF-1 alpha heterozygote mice, respectively. Keywords: ordered

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HIF-1 transcription activity: HIF1A driven response in normoxia and in hypoxia.

Project description:BACKGROUND:HIF1A (Hypoxia-Inducible-Factor 1A) expression in solid tumors is relevant to establish resistance to therapeutic approaches. The use of compounds direct against hypoxia signaling and HIF1A does not show clinical efficiency because of changeable oxygen concentrations in solid tumor areas. The identification of HIF1A targets expressed in both normoxia and hypoxia and of HIF1A/hypoxia signatures might meliorate the prognostic stratification and therapeutic successes in patients with high-risk solid tumors. METHODS:In this study, we conducted a combined analysis of RNA expression and DNA methylation of neuroblastoma cells silenced or unsilenced for HIF1A expression, grown in normoxia and hypoxia conditions. RESULTS:The analysis of pathways highlights HIF-1 (heterodimeric transcription factor 1) activity in normoxia in metabolic process and HIF-1 activity in hypoxia in neuronal differentiation process. HIF1A driven transcriptional response in hypoxia depends on epigenetic control at DNA methylation status of gene regulatory regions. Furthermore, low oxygen levels generate HIF1A-dependent or HIF1A-independent signatures, able to stratify patients according to risk categories. CONCLUSIONS:These findings may help to understand the molecular mechanisms by which low oxygen levels reshape gene signatures and provide new direction for hypoxia targeting in solid tumor.

| S-EPMC6390360 | biostudies-literature

Role of oxygen in fetoplacental endothelial responses: hypoxia, physiological normoxia, or hyperoxia?

Project description:During pregnancy, placental vascular growth, which is essential for supporting the rapidly growing fetus, is associated with marked elevations in blood flow. These vascular changes take place under chronic physiological low O2 (less than 2-8% O2 in human; chronic physiological normoxia, CPN) throughout pregnancy. O2 level below CPN pertinent to the placenta results in placental hypoxia. Such hypoxia can cause severe endothelial dysfunction, which is associated with adverse pregnancy outcomes (e.g., preeclampsia) and high risk of adult-onset cardiovascular diseases in children born to these pregnancy complications. However, our current knowledge about the mechanisms underlying fetoplacental endothelial function is derived primarily from cell models established under atmospheric O2 (~21% O2 at sea level, hyperoxia). Recent evidence has shown that fetoplacental endothelial cells cultured under CPN have distinct gene expression profiles and cellular responses compared with cells cultured under chronic hyperoxia. These data indicate the critical roles of CPN in programming fetal endothelial function and prompt us to re-examine the mechanisms governing fetoplacental endothelial function under CPN. Better understanding these mechanisms will facilitate us to develop preventive and therapeutic strategies for endothelial dysfunction-associated diseases (e.g., preeclampsia). This review will provide a brief summary on the impacts of CPN on endothelial function and its underlying mechanisms with a focus on fetoplacental endothelial cells.

| S-EPMC7294327 | biostudies-literature

Minimal Influence of Hypobaria on Heart Rate Variability in Hypoxia and Normoxia.

Project description:IntroductionThe present study evaluated the putative effect of hypobaria on resting HRV in normoxia and hypoxia.MethodsFifteen young pilot trainees were exposed to five different conditions in a randomized order: normobaric normoxia (NN, PB = 726 ± 5 mmHg, FIO2 = 20.9%), hypobaric normoxia (HN, PB = 380 ± 6 mmHg, FIO2≅40%), normobaric hypoxia (NH, PB = 725 ± 4 mmHg, FIO2≅11%); and hypobaric hypoxia (HH at 3000 and 5500 m, HH3000 and HH5500, PB = 525 ± 6 and 380 ± 8 mmHg, respectively, FIO2 = 20.9%). HRV and pulse arterial oxygen saturation (SpO2) were measured at rest seated during a 6 min period in each condition. HRV parameters were analyzed (Kubios HVR Standard, V 3.0) for time (RMSSD) and frequency (LF, HF, LF/HF ratio, and total power). Gas exchanges were collected at rest for 10 min following HRV recording.ResultsSpO2 decreased in HH3000 (95 ± 3) and HH5500 (81 ± 5), when compared to NN (99 ± 0). SpO2 was higher in NH (86 ± 4) than HH5500 but similar between HN (98 ± 2) and NN. Participants showed lower RMSSD and total power values in NH and HH5500 when compared to NN. In hypoxia, LF/HF ratio was greater in HH5500 than NH, whereas in normoxia, LF/HF ratio was lower in HN than NN. Minute ventilation was higher in HH5500 than in all other conditions.DiscussionThe present study reports a slight hypobaric effect either in normoxia or in hypoxia on some HRV parameters. In hypoxia, with a more prominent sympathetic activation, the hypobaric effect is likely due to the greater ventilation stimulus and larger desaturation. In normoxia, the HRV differences may come from the hyperoxic breathing and slight breathing pattern change due to hypobaria in HN.

| S-EPMC7472461 | biostudies-literature

A Four-Way Comparison of Cardiac Function with Normobaric Normoxia, Normobaric Hypoxia, Hypobaric Hypoxia and Genuine High Altitude.

Project description:BackgroundThere has been considerable debate as to whether different modalities of simulated hypoxia induce similar cardiac responses.Materials and methodsThis was a prospective observational study of 14 healthy subjects aged 22-35 years. Echocardiography was performed at rest and at 15 and 120 minutes following two hours exercise under normobaric normoxia (NN) and under similar PiO2 following genuine high altitude (GHA) at 3,375 m, normobaric hypoxia (NH) and hypobaric hypoxia (HH) to simulate the equivalent hypoxic stimulus to GHA.ResultsAll 14 subjects completed the experiment at GHA, 11 at NN, 12 under NH, and 6 under HH. The four groups were similar in age, sex and baseline demographics. At baseline rest right ventricular (RV) systolic pressure (RVSP, p = 0.0002), pulmonary vascular resistance (p = 0.0002) and acute mountain sickness (AMS) scores were higher and the SpO2 lower (p<0.0001) among all three hypoxic groups (GHA, NH and HH) compared with NN. At both 15 minutes and 120 minutes post exercise, AMS scores, Cardiac output, septal S', lateral S', tricuspid S' and A' velocities and RVSP were higher and SpO2 lower with all forms of hypoxia compared with NN. On post-test analysis, among the three hypoxia groups, SpO2 was lower at baseline and 15 minutes post exercise with GHA (89.3±3.4% and 89.3±2.2%) and HH (89.0±3.1 and (89.8±5.0) compared with NH (92.9±1.7 and 93.6±2.5%). The RV Myocardial Performance (Tei) Index and RVSP were significantly higher with HH than NH at 15 and 120 minutes post exercise respectively and tricuspid A' was higher with GHA compared with NH at 15 minutes post exercise.ConclusionsGHA, NH and HH produce similar cardiac adaptations over short duration rest despite lower SpO2 levels with GHA and HH compared with NH. Notable differences emerge following exercise in SpO2, RVSP and RV cardiac function.

| S-EPMC4839767 | biostudies-literature

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