Human Cytomegalovirus miR-UL70-3p Downregulates the H2O2-Induced Apoptosis by Targeting the Modulator of Apoptosis-1 (MOAP1).
Ontology highlight
ABSTRACT:
SUBMITTER: Pandeya A
PROVIDER: S-EPMC8744590 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:miRNAs are a class of hairpin-derived RNAs, 21-24 nucleotides in length, which are involved in a range of biological processes. The bta-miR-2285 family has over 40 members spanning the entire bovine genome. We previously found that bta-miR-2285o-3p was highly expressed in yak heart and lung when compared with cattle, which prompted us to investigate its potential function in high-altitude adaptation of yaks. In this study, we detected wide-spread high expression of bta-miR-2285o-3p in yak tissues. Further experiments revealed that the protein tyrosine phosphatase receptor type M (PTPRM) gene was the host gene of bta-miR-2285o-3p and that two linked SNPs in bta-mir-2285o precursor affected the biogenesis of mature miRNA (bta-miR-2285o-3p). Functional analysis in vitro indicated that bta-miR-2285o-3p attenuated hypoxia-induced apoptosis by targeting very low-density lipoprotein receptor (VLDLR), phosphatase and tensin homolog (PTEN) and caspase-3. Expression level analysis in vivo revealed the high negative Pearson's correlation between bta-miR-2285o-3p and caspase3 in yak, highlighting the potential important roles of bta-miR-2285o-3p in yak high-altitude adaptation. Our study provides a typical model for deciphering the function of miRNAs in environmental adaptation.
| S-EPMC9298924 | biostudies-literature
Project description:MicroRNAs are short, single-stranded non-coding RNA molecules that function as regulators of tumor progression in various cancers, including glioma. The present study sought to investigate the biological functions of miR-9-3p in glioma progression. The results of a microRNA microarray indicated that microRNA-9-3p (miR-9-3p, miR-9*) is down-regulated in high-grade (grades III and IV) gliomas compared with non-tumor tissues. These results were confirmed with real-time PCR. The miR-9-3p expression level was associated with age and tumor grade. Herpud1 was regulated by miR-9-3p in glioma cells and tissues and was identified as a miR-9-3p target with luciferase reporter assays. Glioma cells transfected with miR-9-3p mimics or HERPUD1-RNAi had more apoptotic cells than them in control after induced by H2O2. Our results indicated that low expression of miR-9-3p results in a high level of Herpud1, which may protect against apoptosis in glioma.
2017-03-28 | GSE97071 | GEO
Project description:Myocardial infarction (MI) is a major type of cardiovascular disorder worldwide. In the present study, we established a new microRNA (miRNA)-mRNA cross-talk network by integrating data obtained from The National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO). In addition, functional assays, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses, were conducted using the Database for Annotation, Visualization, and Integration Discovery (DAVID). In our study, we generated a new differentially expressed miRNA (DEmiRNA)-differentially expressed gene (DEG) cross-talk network of MI composed of three miRNA (miR-489, miR-375, and miR-142-3p) nodes and 163 mRNA nodes. In vitro experiments demonstrated that miR-489 expression was increased in H2O2-treated H9c2 cardiomyocytes in vitro, mimicking myocardial injury. We observed that down-regulation of miR-489 reduced H2O2-induced apoptosis, while overexpression of miR-489 had the opposite effects, as revealed by flow cytometry and Western blot analyses. Furthermore, we confirmed the relationship between miR-489 and IGF1 through double luciferase reporter gene assays, which partly explains the antiapoptotic mechanism of miR-489. In conclusion, the experimental results of the present study could provide important clues for investigating the mechanism of MI.
| S-EPMC7494985 | biostudies-literature
Project description:Sepsis is a complication of infection caused by disease or trauma. Increasing evidence have shown that long noncoding RNAs (lncRNAs) are involved in the regulation of sepsis. However, the mechanism of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in the regulation of sepsis progression remains to be elucidated. Lipopolysaccharide (LPS) was used to induce a sepsis cell model. The expression levels of NEAT1 and microRNA (miR)-590-3p were determined by reverse transcription-quantitative PCR. Cell viability and apoptosis were detected using Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Western blot analysis was performed to evaluate the levels of apoptosis- and NF-κB signaling pathway-related proteins. The concentration of inflammatory cytokines was determined using ELISA. In addition, dual-luciferase reporter assay, RNA immunoprecipitation and biotin-labeled RNA pull-down assay were performed to verify the interaction between NEAT1 and miR-590-3p. The results showed that NEAT1 was highly expressed in patients with sepsis and LPS-induced H9c2 cells. Knockdown of NEAT1 decreased LPS-induced cell apoptosis and inflammation response in H9c2 cells. Meanwhile, miR-590-3p showed decreased expression in sepsis, and its overexpression could relieve LPS-induced H9c2 cell damage. Further experiments revealed that NEAT1 could sponge miR-590-3p. Knockdown of miR-590-3p reversed the inhibitory effect of NEAT1 knockdown on LPS-induced H9c2 cell damage. Additionally, the NEAT1/miR-590-3p axis could regulate the activity of the NF-κB signaling pathway. To conclude, lncRNA NEAT1 accelerated apoptosis and inflammation in LPS-stimulated H9c2 cells via sponging miR-590-3p. These findings may provide a new strategy for the treatment of sepsis.
| S-EPMC7444425 | biostudies-literature
Project description:Programmed cell death 4 (PDCD4) is a novel tumor suppressor gene and a promising target for anticancer therapies. PDCD4 is frequently downregulated in various human cancers; however, the molecular mechanism accounting for the loss expression of PDCD4 in cancers is not fully understood. In this study, we identified specific targeting sites for miR-208a-3p in the 3'-untranslated region (3'-UTR) of the PDCD4 gene which regulated PDCD4 expression. We demonstrated that miR-208a-3p suppressed apoptosis in gastric cancer cells by targeting PDCD4. We also showed that miR-208a-3p promoted the development of tumor growth in xenograft mice by negatively regulating PDCD4. Taken together, this study revealed a critical role for miR-208a-3p as an oncogenic miRNA in gastric carcinogenesis and it may provide a potential novel target for gastric cancer diagnosis and therapy.
| S-EPMC5341878 | biostudies-literature
Project description:Human cytomegalovirus (HCMV) infection of myeloid lineage cells, such as CD34+ hematopoietic progenitor cells (HPCs) or monocytes, results in the upregulation of antiapoptotic cellular proteins that protect the newly infected cells from programmed cell death. The mechanisms used by HCMV to regulate proapoptotic cellular proteins upon infection of CD34+ HPCs have not been fully explored. Here, we show that HCMV utilizes pUL7, a secreted protein that signals through the FLT3 receptor, and miR-US5-1 and miR-UL112-3p to reduce the abundance and activity of the proapoptotic transcription factor FOXO3a at early times after infection of CD34+ HPCs. Regulation of FOXO3a by pUL7, miR-US5-1, and miR-UL112 results in reduced expression of the proapoptotic BCL2L11 transcript and protection of CD34+ HPCs from virus-induced apoptosis. These data highlight the importance of both viral proteins and microRNAs (miRNAs) in protecting CD34+ HPCs from apoptosis at early times postinfection, allowing for the establishment of latency and maintenance of viral genome-containing cells.IMPORTANCE Human cytomegalovirus (HCMV) causes serious disease in immunocompromised individuals and is a significant problem during transplantation. The virus can establish a latent infection in CD34+ hematopoietic progenitor cells (HPCs) and periodically reactivate to cause disease in the absence of an intact immune system. What viral gene products are required for successful establishment of latency is still not fully understood. Here, we show that both a viral protein and viral miRNAs are required to prevent apoptosis after infection of CD34+ HPCs. HCMV pUL7 and miRNAs miR-US5-1 and miR-UL112-3p act to limit the expression and activation of the transcription factor FOXO3a, which in turn reduces expression of proapoptotic gene BCL2L11 and prevents virus-induced apoptosis in CD34+ HPCs.
| S-EPMC7845589 | biostudies-literature
Project description:Radiation-induced central nervous system toxicity is a significant risk factor for patients receiving cancer radiotherapy. Surprisingly, the mechanisms responsible for the DNA damage-triggered neuronal cell death following irradiation have yet to be deciphered. Using primary cortical neuronal cultures in vitro, we demonstrated that X-ray exposure induces the mitochondrial pathway of intrinsic apoptosis and that miR-23a-3p plays a significant role in the regulation of this process. Primary cortical neurons exposed to irradiation show the activation of DNA-damage response pathways, including the sequential phosphorylation of ATM kinase, histone H2AX, and p53. This is followed by the p53-dependent up-regulation of the pro-apoptotic Bcl2 family molecules, including the BH3-only molecules PUMA, Noxa, and Bim, leading to mitochondrial outer membrane permeabilization (MOMP) and the release of cytochrome c, which activates caspase-dependent apoptosis. miR-23a-3p, a negative regulator of specific pro-apoptotic Bcl-2 family molecules, is rapidly decreased after neuronal irradiation. By increasing the degradation of PUMA and Noxa mRNAs in the RNA-induced silencing complex (RISC), the administration of the miR-23a-3p mimic inhibits the irradiation-induced up-regulation of Noxa and Puma. These changes result in an attenuation of apoptotic processes such as MOMP, the release of cytochrome c and caspases activation, and a reduction in neuronal cell death. The neuroprotective effects of miR-23a-3p administration may not only involve the direct inhibition of pro-apoptotic Bcl-2 molecules downstream of p53 but also include the attenuation of secondary DNA damage upstream of p53. Importantly, we demonstrated that brain irradiation in vivo results in the down-regulation of miR-23a-3p and the elevation of pro-apoptotic Bcl2-family molecules PUMA, Noxa, and Bax, not only broadly in the cortex and hippocampus, except for Bax, which was up-regulated only in the hippocampus but also selectively in isolated neuronal populations from the irradiated brain. Overall, our data suggest that miR-23a-3p down-regulation contributes to irradiation-induced intrinsic pathways of neuronal apoptosis. These regulated pathways of neurodegeneration may be the target of effective neuroprotective strategies using miR-23a-3p mimics to block their development and increase neuronal survival after irradiation.
| S-EPMC7279507 | biostudies-literature
Project description:The present study aimed to investigate the association between septin 7 (SEPT7) and melatonin-induced apoptosis in the human fetal osteoblastic cell line hFOB 1.19. MicroRNA (miR)?590?3p was identified by identifying overlapping miRNAs that target SEPT7, across different databases (miRDB, DIANA and Targetscan). Apoptosis was assessed via flow cytometric analysis. Small interfering RNA of SEPT7 and a miR?590?3p inhibitor were used for gene silencing and the efficiency was assessed by reverse transcription?quantitative polymerase chain reaction. Western blotting was used to measure the expression of proteins associated with pathways mediating endoplasmic reticulum stress and melatonin?induced apoptosis. The present study identified that SEPT7 was a potential target of miR?590?3p and demonstrated that SEPT7 is associated with mediating the pro?apoptotic effect of miR?590?3p in human osteoblast cell line hFOB 1.19. High concentrations of melatonin may result in the inhibition of miR?590?3p expression, leading to the upregulation of target genes that promote apoptosis.
| S-EPMC5928678 | biostudies-literature
Project description:The aim of this study was to explore the role of hsa_circRNA_0000205 (circ_0000205) in chondrocyte injury in osteoarthritis (OA) and the underlying mechanism. Expression of circ_0000205, microRNA (miR)-766-3p and a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5 was detected by quantitative real time (qRT)-polymerase chain reaction (PCR) and Western blot assays. Cell proliferation, apoptosis, and extracellular matrix (ECM) synthesis were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and 5-ethynyl-2-deoxyuridine assays, flow cytometry, and qRT-PCR and Western blot assays. The target relationship between miR-766-3p and circ_0000205 or ADAMTS5 was confirmed by luciferase reporter assay and RNA immunoprecipitation. IL-1β treatment could attenuate cell viability of primary chondrocytes and proliferating cell nuclear antigen (PCNA) and collagen II type alpha-1 (COL2A1) levels, and elevate apoptosis rate and cleaved caspase-3, ADAMTS5 and matrix metalloproteinase-13 (MMP13) levels, suggesting that IL-1β induced chondrocyte apoptosis and ECM degradation. Expression of circ_0000205 was up-regulated in OA tissues and IL-1β-induced primary chondrocytes, accompanied with miR-766-3p down-regulation and ADAMTS5 up-regulation. Knockdown of circ_0000205 could mitigate IL-1β-induced above effects and improve cell proliferation. Moreover, both depleting miR-766-3p and promoting ADAMTS5 could partially counteract circ_0000205 knockdown roles in IL-1β-cultured primary chondrocytes. Notably, circ_0000205 was verified as a sponge for miR-766-3p via targeting, and ADAMTS5 was a direct target for miR-766-3p. Silencing circ_0000205 could protect chondrocytes from IL-1β-induced proliferation reduction, apoptosis, and ECM degradation by targeting miR-766-3p/ADAMTS5 axis.
| S-EPMC9058376 | biostudies-literature
Project description:BackgroundOsteoarthritis (OA) is a chronic disease that involves chondrocyte injury and dysfunction. CircRNAs participate in OA progression, but the roles of circRNAs in the occurrence of OA are unclear. In this study, we explore the role of circ_0008365 in OA.MethodsCHON-001 cells were treated with interleukin-1β (IL-1β) to construct an in vitro OA cell model. The levels of circ_0008365, SRY-related high mobility group-box gene9 (SOX9) mRNA, and microRNA-338-3p (miR-338-3p) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Western blot (WB) assay was used to measure protein levels. Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EDU) assay, and flow cytometry analysis were used to detect cell viability, proliferation, and apoptosis, respectively. Dual-luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation (RIP) assays were used to confirm the interaction between miR-338-3p with circ_0008365 or SOX9.ResultsCirc_0008365 expression was reduced in OA tissues and IL-1β-induced CHON-001 cells. Functionally, circ_0008365 inhibited viability, proliferation, and ECM degradation and promoted apoptosis of IL-1β-induced CHON-001 cells. Mechanistically, circ_0008365 acted as a sponge of miR-338-3p to regulate SOX9 expression, thus exerting its functions in IL-1β-induced CHON-001 cells. Moreover, exosomal circ_0008365 had great value in diagnosing OA.ConclusionCirc_0008365 alleviates IL-1β-induced CHON-001 cell damage through the miR-338-3p/SOX9 axis, which suggested that circ_0008365 might be a new therapeutic target for OA.
| S-EPMC9569125 | biostudies-literature