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:Cell cycle arrest in response to DNA damage is an important anti-tumorigenic mechanism. microRNAs (miRNAs) were shown recently to play key regulatory roles in cell cycle progression. For example, miR-34a is induced in response to p53 activation and mediates G1 arrest by down-regulating multiple cell cycle-related transcripts. Here we show that genotoxic stress promotes the p53-dependent up-regulation of the homologous miRNAs, miR -192 and miR-215. Like miR-34a, activation of miR-192/215 induces cell cycle arrest suggesting that multiple microRNA families operate in the p53 network. Furthermore, we define a downstream gene expression signature for miR-192/215 expression that includes a number of transcripts that regulate G1 and G2 checkpoints. Of these transcripts, 18 transcripts are direct targets of miR-192/215 and the observed cell cycle arrest likely results from a cooperative effect among the modulations of these genes by the miRNAs. Our results demonstrating a role for miR-192/215 in cell proliferation combined with recent observations that these miRNAs are under-expressed in primary cancers support the idea that miR-192 and miR-215 function as tumor-suppressors. Description: Transfection of siRNA luc, miR-192 or miR-215 into HCT116 Dicerex5, compared to mock-transfected cells, with mRNA expression profiled at 10h and 24h post-transfection. Species: Human Tissue: HCT116 Dicerex5 cell line (tissue of origin = human colorectal carcinoma); this cell line is hypomorphic for Dicer gene function. Dye-swap: no Negative control: siRNA luc Replicates per each timepoint: no