The identification of genes related to METTL14 overexpression in radiation-induced hepatocyte death based on bioinformatics analysis
Ontology highlight
ABSTRACT:
INSTRUMENT(S): DNBSEQ-T7
ORGANISM(S): Mus musculus
SUBMITTER: wenjun yin
PROVIDER: E-MTAB-16163 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The identification of genes related to METTL14 overexpression in radiation-induced hepatocyte death based on bioinformatics analysis
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Project description:Radiation-induced liver disease (RILD) is a serious complication of radiotherapy for upper abdominal tumors, the cellular and molecular basis of which remain mostly unclear. Sprague‒Dawley (SD) rats were exposed to a single dose of 30 gray (Gy) at a dose rate of 400 cGy/min on the right upper quadrant of the abdomen to induce liver injury in vivo. At 2 weeks after IR, Kupffer cells (KCs) characteristically expressed Il6. IL-6 activated the JAK‒STAT signaling pathway in hepatocytes. However, the critical downstream target genes were unclear.
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Project description:We used microarrays to measure the expression levels of genes in irradiated immortalized B cells, lymphoblastoid cells, from members of Centre d'Etude du Polymorphisme Humain (CEPH) Utah pedigrees. Data were collected for cells at baseline and 2 hours and 6 hours after exposure to 10 Gy of ionizing radiation (IR).
2011-08-04 | GSE26835 | GEO
Project description:We used microarrays to measure the expression levels of genes in irradiated immortalized B cells, lymphoblastoid cells, from members of Centre d'Etude du Polymorphisme Humain (CEPH) Utah pedigrees. Data were collected for cells at baseline and 2 hours and 6 hours after exposure to 10 Gy of ionizing radiation (IR). We measured the expression levels of genes in irradiated immortalized B cells, lymphoblastoid cells, from members of 30 Centre d'Etude du Polymorphisme Humain (CEPH) Utah pedigrees (CEPH 1331, 1332, 1333, 1341, 1344, 1346, 1347, 1349, 1354, 1356, 1357, 1358, 1362, 1408, 1413, 1416, 1418, 1420, 1421, 1423, 1424, 1444, 1447, 1451, 1454, 1456, 1458, 1463, 1477, 1582). Cells were irradiated at 10 Gy in a 137Cs irradiator. Cells were harvested prior to radiation and at 2 and 6 hours following exposure to IR.
2011-08-03 | E-GEOD-26835 | biostudies-arrayexpress
Project description:Mettl14, a key component of the m6A methyltransferase complex, plays a crucial role in regulating mRNA stability and splicing. Reduced expression of Mettl14 is associated with hepatocellular carcinoma and liver regeneration, yet the molecular mechanisms by which it regulates the hepatocyte cell cycle remain unclear. Using RNA-Seq and MeRIP-Seq in liver-specific Mettl14 knockout mice, we found that Mettl14 deficiency stabilizes Fam32a mRNA through m6A modifications, resulting in increased Fam32a protein levels. Elevated Fam32a expression accelerates the G1/S transition by modulating Cdkn1a splicing, specifically downregulating its variant 2. These findings uncover a novel m6A-dependent mechanism that regulates hepatocyte cell cycle progression and highlight the previously unrecognized role of Fam32a in promoting the G1/S transition.
2025-03-31 | GSE293314 | GEO
Project description:Purpose: The International Commission on Radiological Protection (ICRP) recently recommended reducing the occupational equivalent dose limit for the lens of the eye. Based primarily on a review of epidemiological data, the absorbed dose threshold is now considered to be 0.5 Gy for induction of acute opacities, reduced from the previous threshold of 2 Gy. However, direct mechanistic evidence to support an understanding of the underlying molecular mechanisms of damage is still lacking. To this end, we explored the effects of a broad dose-range of ionizing radiation exposure on gene expression changes in a human lens epithelial (HLE) cell-line in order to better understand the shape of the dose-response relationship and identify transcriptional thresholds of effects. Methods: HLE cells were exposed to doses of 0, 0.01, 0.05, 0.25, 0.5, 2, and 5 Gy of X-ray radiation at two dose rates (1.62 cGy/min and 38.2 cGy/min). Cell culture lysates were collected 20 h post-exposure and analysed using whole-genome RNA-sequencing. Pathways and dose-thresholds of biological effects were identified using benchmark dose (BMD) modeling. Results: Transcriptional responses were minimal at doses less than 2 Gy. At higher doses there were a significant number of differentially expressed genes (DEGs) (p < 0.05, fold change > |1.5|) at both dose rates, with 1308 DEGs for the low dose rate (LDR) and 840 DEGs for the high dose rate (HDR) exposure. Dose-response modeling showed that a number of genes exhibited non-linear bi-phasic responses, which was verified by digital droplet PCR. BMD analysis showed the majority of the pathways responded at BMD median values in the dose range of 1.5-2.5 Gy, with the lowest BMD median value being 0.6 Gy for the HDR exposure. The minimum pathway BMD median value for LDR exposure, however, was 2.5 Gy. Although the LDR and HDR exposures shared pathways involved in extracellular matrix reorganization and collagen production with BMD median value of 2.9 Gy, HDR exposures were more effective in activating pathways associated with DNA damage response, apoptosis, and cell cycling relative to LDR exposure. Conclusion: Overall, the results suggest that radiation induces complex non-linear transcriptional dose-response relationships that are dose-rate dependent. Pathways shared between the two dose rates may be important contributors to radiation-induced cataractogenesis. BMD analysis suggests that the majority of pathways are activated above 0.6 Gy, which supports current ICRP identified dose thresholds for deterministic effects to the lens of the eye of 0.5 Gy.
2018-10-04 | GSE120805 | GEO
Project description:The effect of radiation therapy on tumor vasculature has long been a subject of debate. Increased oxygenation and perfusion have been documented during radiation treatments. Conversely, apoptosis of irradiated tumor endothelial cells has been proposed as a major determinant of tumor control. To approach these contradictions, we used multiphoton microscopy in two murine tumor models: MC38, a highly vascularized and B16F10, a moderately vascularized model, grown in transgenic mice with tdTomato labelled endothelium. These tumors received either a single dose of radiation (15 Gy) or a fractionated dose (5x3 Gy). Unexpectedly, even these high doses led to little structural change of the perfused vasculature. However, non-perfused vessels and blind ends were substantially impaired after radiation accompanied by apoptosis of their endothelium. Additionally, proliferation of endothelium was blocked. Further, RNAseq confirmed the modification of gene expression in apoptotic and cell cycle regulation pathways. Therefore, we show that apoptosis of tumor endothelial cells after radiation does not impair vascular structure.
2022-07-13 | GSE168481 | GEO
Project description:The impact of low-dose ionizing radiation (IR) on human brain has recently attracted attention due to increased use of IR for diagnostic purposes. The aim of this study was to investigate low-dose radiation response in hippocampus. Female C57Bl/6 mice were irradiated with 0 (control), 0.063, 0.125 or 0.5 Gy and quantitative label-free proteomic analysis of hippocampus was performed after 24 months. Key pathways were validated by immunoblotting. CREB signaling and CREB-associated pathways were the most affected ones at all doses. The two lower doses seemed to induce CREB pathway, whereas the exposure to 0.5 Gy deactivated CREB. Similarly, the lowest dose (0.063 Gy) was anti-inflammatory reducing the number of activated microglia (IBA1), whilst induction of activated microglia and reactive astroglia (GFAP) was found at 0.5 Gy suggesting increased inflammation and astrogliosis, respectively. Apoptotic markers BAX and cleaved CASP-3 and oxidative stress markers (carbonylation, NRF-2) were increased only at the highest dose. Since activated CREB pathway plays a central role in learning and memory, these data suggest neuroprotection at the lowest dose (0.063 Gy) but neurodegeneration at 0.5 Gy. These effects become significant only in old animals (24 m) and support the hypothesis of radiation-induced accelerated aging in the brain.
2019-11-06 | PXD015729 | Pride
Project description:Dose-dependent (phospho) proteome responses of mouse embyronic stem cells to ionising radiation. Quantitative SILAC- and mass spectrometry-based proteomics and phosphoproteomics experiments were performe at half an hour (0.5h) and four hours (4h) after exposure to LD (0.1 Gy) and high doses (HD; 1 Gy) of IR.
2022-03-18 | PXD025343 | Pride
Project description:A set of changes is identified in the transcription profile associated with the long-term, but not the acute, response to radiation exposure. The study was performed in vivo using zebrafish. To study the long-term response, 24 hour post-fertilization embryos were exposed to 0.1 Gy (low dose) or 1.0 Gy (moderate dose) of whole-body gamma radiation and allowed to develop for 16 weeks. Liver mRNA profiles were then analyzed using the Affymetrix microarray platform, with validation by quantitative PCR. To be able to compare this to the acute response, 16-week old adults were exposed at the same doses and analyzed after 4 hours. We used 5 treatment groups: A=non-irradiated control, allowed to develop for 16 weeks; B=low-dose (0.1 Gy) irradiated, allowed to develop for 16 weeks; C=high-dose (1.0 Gy) irradiate, allowed to develop for 16 weeks; D=16 week old adults irradiated at low dose (0.1 Gy); E=16 week old adults irradiate at high dose (1.0 Gy)
2014-04-01 | E-GEOD-46026 | biostudies-arrayexpress