CXCR4/miR-1910-5p/MMRN2 Axis is Involved in Corneal Neovascularization by Affecting Vascular Permeability
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE226185 | GEO | 2023/04/26
REPOSITORIES: GEO
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Project description:PurposeChemokine receptor 4 (CXCR4) plays an essential role in the early stage of corneal neovascularization (CNV), but the underlying key molecular mechanism has yet to be addressed. This study aimed to explore the new molecular mechanism of CXCR4 in CNV and the related pathological events.MethodsCXCR4 was assayed by immunofluorescence or Western blotting. The function of the supernatant from hypoxia-treated human corneal epithelial cells (HCE-T) cells was examined by culturing with human umbilical vein endothelial cells. MicroRNA sequencing was used to detect the downstream microRNAs upon CXCR4 knockdown and analyzed by preliminary bioinformatics. The proangiogenic functions and downstream target genes of microRNA were investigated by gene interference and luciferase assay. An alkali-burned murine model was introduced to examine the function and mechanism of miR-1910-5p in vivo.ResultsHigh CXCR4 expression was confirmed in corneal tissues of patients with CNV and hypoxic HCE-T cells. The supernatant from hypoxia-treated HCE-T cells is involved in the CXCR4-mediated angiogenesis of human umbilical vein endothelial cells. Notably, miR-1910-5p was demonstrated to be at a high level in wild-type HCE-T cells and its supernatant, and in CNV patient tears. The proangiogenic functions of miR-1910-5p were demonstrated with the assays of cell migration, tube formation, and aortic ring. Moreover, miR-1910-5p significantly inhibited multimerin-2 expression by targeting its 3' untranslated region and caused significant extracellular junctional defects in human umbilical vein endothelial cells. MiR-1910-5p antagomir could significantly increase multimerin-2 level and decrease vascular leakage, and ultimately inhibit CNV in a murine model.ConclusionsOur results revealed a novel CXCR4-mediated mechanism and proved that targeting the miR-1910-5p/multimerin-2 pathway could be a promising therapeutic target for CNV.
| S-EPMC10108737 | biostudies-literature
Project description:CXCR4/miR-1910-5p/MMRN2 Axis is Involved in Corneal Neovascularization by Affecting Vascular Permeability
| PRJNA939144 | ENA
Project description:The goal of this study was to identify signalling molecules downstream of CXCR4 in breast cancer cells. For this purpose, we sorted CXCR4-positive and CXCR4-negative cells from MDA-MB-231 breast cancer cell line by flow cytometry and performed microarrays analysis. Three sets of samples, each in quadruplicate, were analyzed. These include CXCR4-positive subpopulation, CXCR4-positive subpopulation treated with SDF-1 (ligand for CXCR4, also called CXCL12) for one hour and CXCR4-negative subpopulation.
2010-04-28 | E-GEOD-15893 | biostudies-arrayexpress
Project description:The goal of this study was to identify signaling molecules downstream of CXCR4 in breast cancer cells. For this purpose, we sorted CXCR4-positive and CXCR4-negative cells from MDA-MB-231 breast cancer cell line by flow cytometry and performed microarrays analysis.
2010-04-20 | GSE15893 | GEO
Project description:Antibodies and derivative drugs targeting immune checkpoints have been approved for the treatment of several malignancies, but there are fewer responses in patients with pancreatic cancer. Here, we designed a nanobody molecule with bi-targeting on PD-L1 and CXCR4, as both targets are overexpressed in many cancer cells and play important roles in tumorigenesis. The nanobody sequences targeting PD-L1 and CXCR4 were linked by the (G4S)3 flexible peptide to construct the anti-PD-L1/CXCR4 bispecific nanobody. The bispecific nanobody was expressed in E. coli cells and purified by affinity chromatography. The purified nanobody was biochemically characterized by mass spectrometry, Western blotting and flow cytometry to confirm the molecule and its association with both PD-L1 and CXCR4. The biological function of the nanobody and its anti-tumour effects were examined.
2023-03-11 | PXD037102 | Pride
Project description:To investigate the gene expression in human corneal epithelial overexpressing hsa-miR-145 by transfection , we have employed Whole Human Genome Oligo Microarray (Agilent) as a screening platform to identify gene regulation. We discovered a differential gene expression in HCE cells transfected with hsa-mIR-145 against cells with scrambled sequences. Among them, genes related with corneal development, integrity, differentiation and inflammatory responses were found and this was validated by real-time PCR. HCE cells transfected with hsa-miR-145 or scrambled sequences were collected at 24 hours after transfection. Total RNA was extracted by Trizol/chloroform and purified with RNeasy mini spin column. RNA samples with 28S/18S ratios in the range of 1.4 to 1.8 were used for expression RNA profiling using Whole Human Genome Oligo Microarray (Agilent).
2011-10-09 | E-GEOD-24980 | biostudies-arrayexpress
Project description:Surface expression of C-X-C chemokine receptor type 4 (CXCR4) in acute myeloid leukemia (AML) has been reported to be an independent prognostic factor for disease relapse and survival. We previously reported that targeting the stromal-derived factor 1M-NM-1 (SDF-1M-NM-1)/CXCR4 axis could overcome resistance of AML cells to chemotherapy both in vitro and in vivo. To further explore the mechanism of targeting CXCR4, in the current study we focused on the regulation of microRNA. Microarray analysis revealed that the hsa-let-7a microRNA was down-regulated in OCI-AML3 cells by SDF-1M-NM-1 treatment and increased after CXCR4 inhibition. To further investigate the role of hsa-let-7a in leukemia biology, we overexpressed it in AML cell lines, which resulted in decreased Bcl-xL protein expression and consequently enhanced cell sensitivity to the chemotherapeutic agent cytarabine, both in vitro and in vivo. We also identified the transcription factor Yin Yang 1 (YY1) as a mediator that links the SDF-1M-NM-1/CXCR4 axis with hsa-let-7a. Western blotting and immunocytochemistry demonstrated a correlation between YY1 and CXCR4 activation. ChIP assay confirmed the binding of YY1 to pri-let-7a DNA fragments. In primary AML samples (n=50), high CXCR4 surface expression was associated with low hsa-let-7a levels (r2=0.53). Improved effects of cytarabine treatment associated with greatly extended survival of human AML carrying mice was observed in primary human AML overexpressing hsa-let-7a. On the basis of these results, we propose that CXCR4 regulation of hsa-let-7a microRNA through YY1 and transcriptional silencing of the Bcl-xL protein together identifies a novel mechanism by which CXCR4 functions to induce chemoresistance in AML cells. MicroRNA expression profiling of OCI-AML3 cell lines treated with CXCR4 antagonist or SDF-1M-NM-1. OCI-AML3 cells were treated with 100 ng/mL SDF-1M-NM-1 or 250 nM POL6326 (a CXCR4 antagonist, Allschwil, Switzerland), total RNA was extracted at specific time points (1, 2, 4, and 8 h), and miRNA expression profiling was performed
2013-12-01 | E-GEOD-44828 | biostudies-arrayexpress
Project description:Transcriptional profiling of human iPS cells, CECSi cells and iPS-derived neural crest cells (NCC) comparing human corneal endothelial cells (HCE)
2021-06-18 | GSE178434 | GEO
Project description:A dual biomarker signature extracted a stage-specific cytotype according to cell surface expression of CXCR4/FLK-1 after 5 days of spontaneous differentiation from pluripotent stem cells. Genome-wide microarray analysis revealed a high degree of similarity between CXCR4+/FLK-1+ and CXCR4-/FLK-1- subpopulations at day 5, yet the divergent gene expression profile represents more than 700 unique transcripts. Functional analysis of the 294 up-regulated and 440 down-regulated transcripts that distinguished CXCR4+/Flk-1+ from CXCR4-/Flk-1- subpopulations identified an overt ontologic prioritization of “Cardiovascular Development”-IPA 7.0, 2009.Thus, a biomarker-selected subpopulation from spontaneously differentiated pluripotent stem cells identifies a pool of genes that non-stochastically integrate into a blueprint providing instructions for cardiac lineage-specification. Keywords: Comparison of day 5 embryonic stem cell progenity: CXCR4/FLK-1 biomarker positive versus biomarker negative cells Differentiating embryonic stem cells were FACS sorted at day 5 based on a dual CXCR4/FLK-1 biomarker signature and double positive and double negative progeny were thus collected. Day 5 sorted progeny were independently collected to provide raw material for three biological replicates for each experimental condition. In this manner, three CXCR4/FLK-1 double positive biological samples, and three CXCR4/FLK-1 double negative biological samples were obtained. Total RNA was extracted from each of the samples and RNA pools were profiled on Affymetrix Mouse 430 2.0 Arrays to identify global gene expression changes between double positive and double negative progeny at day 5 of differentiation.
2011-03-11 | E-GEOD-20841 | biostudies-arrayexpress
Project description:A dual biomarker signature extracted a stage-specific cytotype according to cell surface expression of CXCR4/FLK-1 after 5 days of spontaneous differentiation from pluripotent stem cells. Genome-wide microarray analysis revealed a high degree of similarity between CXCR4+/FLK-1+ and CXCR4-/FLK-1- subpopulations at day 5, yet the divergent gene expression profile represents more than 700 unique transcripts. Functional analysis of the 294 up-regulated and 440 down-regulated transcripts that distinguished CXCR4+/Flk-1+ from CXCR4-/Flk-1- subpopulations identified an overt ontologic prioritization of “Cardiovascular Development”-IPA 7.0, 2009.Thus, a biomarker-selected subpopulation from spontaneously differentiated pluripotent stem cells identifies a pool of genes that non-stochastically integrate into a blueprint providing instructions for cardiac lineage-specification. Keywords: Comparison of day 5 embryonic stem cell progenity: CXCR4/FLK-1 biomarker positive versus biomarker negative cells
2011-03-11 | GSE20841 | GEO