Mus musculus breed:C57BL/6
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA755951 | ENA |
REPOSITORIES: ENA
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Project description:Infantile hemangiomas (IHs) are commonly observed benign tumors that can cause serious complications.In this study, we investigated the role of M2 macrophage-derived exosomal lncRNA MIR4435-2HG in IHs. Exosomes derived from M2 polarized macrophages were extracted. Next, using cell co-culture or transfection, we investigated whether M2 polarized macrophage-derived exosomes (M2-exos) can transport MIR4435-2HG to regulate the proliferation, migration, invasion, and angiogenesis of hemangioma-derived endothelial cells (HemECs). RNA-seq and RNA pull-down assays were performed to identify targets and regulatory pathways of MIR4435-2HG. We explored the possible mechanisms through which MIR4435-2HG regulates the biological function of HemECs.We found that M2-exos significantly enhanced the proliferation, migration, invasion, and angiogenesis of HemECs. Thus, HemECs uptake M2-exos and promote biological functions through the inclusion of MIR4435-2HG. RNA-seq and RNA pull-down experiments confirmed that MIR4435-2HG regulates of HNRNPA1 expression and directly binds to HNRNPA1, consequently affecting the NF-κB signal pathway.In conclusion, MIR4435-2HG of M2-exos promotes the progression of IHs and enhances the proliferation, migration, invasion, and angiogenesis of HemECs by directly binding to HNRNPA1. This study not only reveals the mechanism of interaction between M2 macrophages and HemECs, but also provides a promising therapeutic target for IHs.
2023-10-29 | GSE236203 | GEO
Project description:In rodent liver, a single injection of N-nitrosodiethylamine (DEN) followed by chronic treatment with the antiepileptic drug phenobarbital (PB) promotes the outgrowth of hepatocellular tumors with activating mutations in Ctnnb1, encoding the transcription factor β-catenin. We now studied long-term effects of PB treatment in livers of transgenic mice with hepatocyte-specific knockout (KO) of Apc, a negative regulator of β-catenin signaling. The number of Apc KO hepatocytes present in the liver decreased with age, indicative of a selective disadvantage of Apc KO cells in the absence of PB. Following liver tumor promotion by PB in Apc KO mice for 9 months, tumor burden was quantified and histological appearance, gene expression profiles, and activity of oncogenic signaling pathways of the tumors were analyzed. In Apc KO mice fed with PB, we observed an increased hepatic tumor volume fraction and tumor multiplicity, as compared to non-promoted animals. Tumors in the PB-treated Apc KO group were mostly eosinophilic hepatocellular adenoma with activated β-catenin, due to the deletion of Apc. These tumors exhibited striking phenotypic similarities to DEN-induced Ctnnb1-mutated tumors, regarding histological appearance and expression of marker proteins and mRNAs. A particular sub-population of tumors, Apc KO-driven basophilic hepatocellular carcinomas, exclusively appeared in the non-PB-treated group but was absent from PB-promoted livers. In conclusion, phenobarbital promotes the outgrowth of Apc-deficient, β-catenin-activated hepatocellular adenoma while simultaneously inhibiting the formation of a certain population of Apc-driven hepatocellular carcinoma.
2018-05-17 | GSE68969 | GEO
Project description:B-cell acute lymphoid leukemias (B-ALL) are the most common neoplastic diseases in children. Survival rates in Hispanics are lower than in non-Hispanic children. It is, therefore, necessary to find predictive and prognostic biomarkers of relapse and death in this population. Our aim was to identify biomarkers of treatment response, which may also predict relapse and death, through identifying differentially expressed and methylated genes between patients who responded or did not respond to induction treatment. DNA and RNA samples were extracted from 27 bone marrow samples from Hispanic children newly diagnosed with B-ALL. mRNA was sequenced using the NextSeq550 Illumina platform. Bisulfite-treated DNA was annealed to Illumina Infinium EPIC Methylation chips. Gene expression and differential methylation were compared between responders and non-responders at day 15 and at the end of induction chemotherapy. DAPK1, CNKSR3, MIR4435-HG2, CTHRC1, NPDC1, SLC45A3, ITGA6, and ASCL2 were overexpressed and hypomethylated in non-responders. The overexpression of MIR4435-2HG, DAPK1, ASCL2, SCL45A3, CNKSR3, and NPDC1 can predict non-response at day 15 and refractoriness. Additionally, higher expression of MIR4435-2HG increases the probability of non-response, death, and the risk of death. DAPK1, CNKSR3, and MIR4435-2HG are also overexpressed in relapse samples. Finally, MIR4435-2HG overexpression, together with positive minimal residual disease, is associated with poorer survival, and together with high expression of DAPK1 and ASCL2, it could improve the risk classification of patients with normal karyotype. In conclusion, MIR4435-2HG is a potential predictive biomarker in children with B-ALL, and its detection at diagnosis could improve survival rates in our patients.
2024-05-22 | GSE229052 | GEO
Project description:B-cell acute lymphoid leukemias (B-ALL) are the most common neoplastic diseases in children. Survival rates in Hispanics are lower than in non-Hispanic children. It is, therefore, necessary to find predictive and prognostic biomarkers of relapse and death in this population. Our aim was to identify biomarkers of treatment response, which may also predict relapse and death, through identifying differentially expressed and methylated genes between patients who responded or did not respond to induction treatment. DNA and RNA samples were extracted from 28 bone marrow samples from Hispanic children newly diagnosed with B-ALL. mRNA was sequenced using the NextSeq2000 Illumina platform. Bisulfite-treated DNA was annealed to Illumina Infinium EPIC Methylation chips. Gene expression and differential methylation were compared between responders and non-responders at day 15 and at the end of induction chemotherapy. DAPK1, CNKSR3, MIR4435-HG2, CTHRC1, NPDC1, SLC45A3, ITGA6, and ASCL2 were overexpressed and hypomethylated in non-responders. The overexpression of MIR4435-2HG, DAPK1, ASCL2, SCL45A3, CNKSR3, and NPDC1 can predict non-response at day 15 and refractoriness. Additionally, higher expression of MIR4435-2HG increases the probability of non-response, death, and the risk of death. DAPK1, CNKSR3, and MIR4435-2HG are also overexpressed in relapse samples. Finally, MIR4435-2HG overexpression, together with positive minimal residual disease, is associated with poorer survival, and together with high expression of DAPK1 and ASCL2, it could improve the risk classification of patients with normal karyotype. In conclusion, MIR4435-2HG is a potential predictive and prognostic biomarker in children with B-ALL, and its detection at diagnosis could improve survival rates in our patients
2024-05-22 | GSE229046 | GEO
Project description:Background: suitable diagnostic markers for cancers are urgently required in clinical practice. Long noncoding RNAs, which have been reported in many cancer types, are a potential new class of biomarkers for tumor diagnosis. Method: LncRNA gene expression profiles were analyzed in two pairs of human gastric cancer and adjacent non-tumor tissues by microarray analysis. Nine gastric cancer-associated lncRNAs were selected and assessed by quantitative real-time polymerase chain reaction in gastric tissues, and 5 of them were further analyzed in gastric cancer patients’plasma. Results: Five lncRNAs, including AK001058, INHBA-AS1, MIR4435-2HG, UCA1 and CEBPA-AS1 were validated to be increased in gastric cancer tissues. Furthermore, we found that plasma level of these five lncRNAs were significantly higher in gastric cancer patients compared with normal controls. By receiver operating characteristic analysis, we found that the combination of plasma lncRNAs with the area under the curve up to 0.921, including AK001058, INHBA-AS1, MIR4435-2HG, and CEBPA-AS1, is a better indicator of gastric cancer than their individual levels or other lncRNA combinations. Simultaneously, we found that the expression levels of a series of MIR4435-2HG fragments are different in gastric cancer plasma samples, but most of them higher than that in healthy control plasma samples. Conclusion: Our results demonstrate that certain lncRNAs, such as AK001058, INHBA-AS1, MIR4435-2HG, and CEBPA-AS1, are enriched in human gastric cancer tissues and significantly elevated in the plasma of patients with gastric cancer. These findings indicate that the combination of these four lncRNAs might be used as diagnostic or prognostic markers for gastric cancer patients.
2017-01-12 | GSE93512 | GEO
Project description:Restriction of HIV-1 replication in elite controllers (ECs) is frequently attributed to T cell-mediated immune responses, while the specific contribution of innate immune cells is less clear. Here, we demonstrated an upregulation of the host long non-coding RNA (lncRNA) MIR4435-2HG in primary myeloid dendritic cells (mDc) from ECs. Elevated expression of this lncRNA in mDCs was associated with a distinct immunometabolic profile, characterized by increased oxidative phosphorylation and glycolysis activities in response to TLR3 stimulation. Using functional assays, we showed that MIR4435-2HG directly influenced the metabolic state of mDCs, likely through epigenetic mechanisms involving H3K27ac enrichment at an intronic enhancer in the RPTOR gene locus, the main component of the mammalian target of rapamycin complex 1 (mTORC1). Together, these results suggested a role of MIR4435-2HG for enhancing immunometabolic activities of mDCs in ECs through targeted epigenetic modifications of a member of the mTOR signaling pathway.
2021-05-03 | GSE167564 | GEO
Project description:Restriction of HIV-1 replication in elite controllers (ECs) is frequently attributed to T cell-mediated immune responses, while the specific contribution of innate immune cells is less clear. Here, we demonstrated an upregulation of the host long non-coding RNA (lncRNA) MIR4435-2HG in primary myeloid dendritic cells (mDc) from ECs. Elevated expression of this lncRNA in mDCs was associated with a distinct immunometabolic profile, characterized by increased oxidative phosphorylation and glycolysis activities in response to TLR3 stimulation. Using functional assays, we showed that MIR4435-2HG directly influenced the metabolic state of mDCs, likely through epigenetic mechanisms involving H3K27ac enrichment at an intronic enhancer in the RPTOR gene locus, the main component of the mammalian target of rapamycin complex 1 (mTORC1). Together, these results suggested a role of MIR4435-2HG for enhancing immunometabolic activities of mDCs in ECs through targeted epigenetic modifications of a member of the mTOR signaling pathway.
2021-05-03 | GSE167563 | GEO