Project description:MicroRNAs are a class of non-coding short-chained RNAs that control cellular functions by downregulating their target genes. Recent research indicates that microRNAs play a role in the maintenance of gut homeostasis. miR-215 was found to be highly expressed in epithelial cells of the small intestine; however, the involvement of miR-215 in gut immunity remains unknown. Here, we show that miR-215 negatively regulates inflammation in the small intestine by inhibiting CXCL12 production. Mice lacking miR-215 showed high susceptibility to inflammation induced by indomethacin, accompanied by an increased number of Th17 cells in the lamina propria of the small intestine. Our findings support a promising perspective of targeting miR-215 to treat inflammatory conditions in the small intestine.
Project description:Interferon-alpha (IFNα) plays a ciritical role in immune regulation, especially in tumor microenvironment. Our previous study has demonstrated that IFNα promoted immunosuppression formation in head and neck squamous cell carcinoma. To explore the mechanism underlying IFNα-induced immunosuppression, long noncoding RNA (lncRNA) sequece was conduted. We identified a novel IFNα-induced upregulated lncRNA, lncMX1-215 in HNSCC. It was mainly located in cell nucleus. Ectopic expression of lncMX1-215 markedly inhibited IFNα-induced immunosuppression molecules, programmed cell death 1 ligand 1(PD-L1) and galectin-9 expression, and vice versa. Subsequently, histone deacetylase (HDAC) inhibitors promoted the expression of PD-L1 and galectin-9. There were binding sites of H3K27 acetylation on PD-L1 and galectin-9 promoters. Mechanically, we find that lncMX1-215 directly interacted with GCN5, a known H3K27 acetylase to interrupt its binding to H3K27 acetylation. Clinically, negative correlations between lncMX1-215 and PD-L1, galectin-9 were observed. Finally, overexpression of lncMX1-215 suppressed the proliferation and metastasis capacity in vitro and in vivo in HNSCC. Our results suggest that lncMX1-215 negatively regulates immunosuppression through interrupting GCN5/H3K27ac in HNSCC and provides novel insights into immune checkpoint blockade treatment.
Project description:Comparison of gene expression in pterygium fibroblast cells after 24 h treatment with hsa-miR-215 mimic or non-specific oligonucleotide control 100nM miR-215 mimic (Thermo Scientific) or non-specific control oligonucleotides are added to cultured fibroblast cells for 24 hours
Project description:We identified a Mariner transposase helix-turn-helix (HTH) DNA-binding domain that was captured in the Caenorhabditis genus by a subset of F-box genes, which we refer to as F-box A2 genes. The origin of F-box A2 genes likely occurred through a single transposase capture event, followed by an increase in copy number. We focused on fbxa-215, a F-box A2 gene highly expressed in the C. elegans germline and embryos, and that localizes to germ granules in embryos. The HTH domain of FBXA-215 is required for fertility and displays predominantly a signature of purifying selection, highlighting the importance of this domain. As the HTH domain of FBXA-215 is related to the DNA-binding HTH domain of transposases, we reasoned that FBXA-215 may bind to DNA in C. elegans and thus regulate gene expression at the transcriptional level. We performed mRNA sequencing of young adults and embryos to test this, but found no clear deregulation of protein-coding genes and transposable elements upon complete deletion of fbxa-215.
Project description:We identified a Mariner transposase helix-turn-helix (HTH) DNA-binding domain that was captured in the Caenorhabditis genus by a subset of F-box genes, which we refer to as F-box A2 genes. The origin of F-box A2 genes likely occurred through a single transposase capture event, followed by an increase in copy number. We focused on fbxa-215, a F-box A2 gene highly expressed in the C. elegans germline and embryos, and that localizes to germ granules in embryos. The HTH domain of FBXA-215 is required for fertility and displays predominantly a signature of purifying selection, highlighting the importance of this domain. As the HTH domain of FBXA-215 is related to the DNA-binding HTH domain of transposases, we reasoned that FBXA-215 may bind to DNA in C. elegans and thus regulate gene expression at the transcriptional level. We performed mRNA sequencing of young adults and embryos to test this, but found no clear deregulation of protein-coding genes and transposable elements upon complete deletion of fbxa-215.
Project description:Comparison of gene expression in pterygium fibroblast cells after 24 h treatment with hsa-miR-215 mimic or non-specific oligonucleotide control