MicroRNA-155 expression suggests a sex disparity in innate lymphoid cells at the single-cell level.
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ABSTRACT:
SUBMITTER: Malmhall C
PROVIDER: S-EPMC7193614 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:MicroRNA-155 (miR-155) has been as an important controller of TLR3 signalling. However, the interactions between miR-155 and TLR3 are poorly understood. Here, we focused on the regulation of the relationship between miR-155 and TLR3. Sequence analyses and firefly luciferase reporter assay revealed that miR-155 target were present in the coding sequences (CDS) of TLR3. And the expression of the TLR3 protein could be inhibited by a miR-155 mimic or by a virally encoded orthologue in chick embryo fibroblast cells. Notably, endogenous miR-155 induction emerged a negative regulation on TLR3 expression in TLR2, 4 and 7 ligands stimulated HD11 cells, an avian macrophage cell line. Moreover, treatment with the miR-155 antagomir increased TLR3 levels while significantly decreased the abundance of TLR3 with miR-155 agomir. In addition, our data showed that miR-155 could inhibit IFN-β production possibly though TLR3 signal pathway. All these findings might reveal a new mechanism by which miR-155 can regulate the TLR3 immune response.
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Project description:Innate lymphoid cells are central to the regulation of immunity at mucosal barrier sites, with group 2 innate lymphoid cells (ILC2s) being particularly important in type 2 immunity. In this study, we demonstrate that microRNA(miR)-142 plays a critical, cell-intrinsic role in the homeostasis and function of ILC2s. Mice deficient for miR-142 expression demonstrate an ILC2 progenitor-biased development in the bone marrow, and along with peripheral ILC2s at mucosal sites, these cells display a greatly altered phenotype based on surface marker expression. ILC2 proliferative and effector functions are severely dysfunctional following Nippostrongylus brasiliensis infection, revealing a critical role for miR-142 isoforms in ILC2-mediated immune responses. Mechanistically, Socs1 and Gfi1 expression are regulated by miR-142 isoforms in ILC2s, impacting ILC2 phenotypes as well as the proliferative and effector capacity of these cells. The identification of these novel pathways opens potential new avenues to modulate ILC2-dependent immune functions.
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Project description:BackgroundChordoma pathogenesis remains poorly understood. In this study, we aimed to evaluate the relationships between microRNA-155 (miR-155) expression and the clinicopathological features of chordoma patients, and to evaluate the functional role of miR-155 in chordoma.MethodsThe miRNA expression profiles were analyzed using miRNA microarray assays. Regulatory activity of miR-155 was assessed using bioinformatic tools. miR-155 expression levels were validated by reverse transcription-polymerase chain reaction. The relationships between miR-155 expression and the clinicopathological features of chordoma patients were analyzed. Proliferative, migratory and invasive activities were assessed by MTT, wound healing, and Matrigel invasion assays, respectively.ResultsThe miRNA microarray assay revealed miR-155 to be highly expressed and biologically active in chordoma. miR-155 expression in chordoma tissues was significantly elevated, and this expression correlated significantly with disease stage (p = 0.036) and the presence of metastasis (p = 0.035). miR-155 expression also correlated significantly with poor outcomes for chordoma patients (hazard ratio, 5.32; p = 0.045). Inhibition of miR-155 expression suppressed proliferation, and the migratory and invasive activities of chordoma cells.ConclusionsWe have shown miR-155 expression to independently affect prognosis in chordoma. These results collectively indicate that miR-155 expression may serve not only as a prognostic marker, but also as a potential therapeutic target in chordoma.
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Project description:MiR-155-5p is a key oncogenic microRNA that maintains immune homeostasis and mediates cross-talk between inflammation and tumorigenesis. High expression of programmed death ligand-1 (PD-L1) also plays an important role in immune tolerance in tumors. The present study aimed to explore the relationship between miR-155-5p and PD-L1 in lung adenocarcinoma (LUAD) cells A549 and H1650. The expression levels of miR-155-5p and PD-L1 in LUAD patients were detected by a quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and mimics of miR-155-5p were used to model increased expression in A549 or H1650 cells. After 24 h, we measured levels of PD-L1 by qRT-PCR, western blotting and flow cytometry. In addition, we identified two sites in the PD-L1 3'-UTR (5'-AGCAUUA-3' and 5'-GCAUUAA-3') that can be bound by miR-155-5p using TargetScan (http://www.targetscan.org). Compared to normal tissue, miR-155-5p was overexpressed in tumor tissue (P = 0.0456), whereas the expression of PD-L1 was not significantly different (P = 0.1349). The expression levels of miR-155-5p and PD-L1 were negatively correlated (r = -0.6409, P = 0.0459 and r = -0.7544, P = 0.0117). Exogenous overexpression of miR-155-5p decreased the mRNA, total protein and membrane protein expression levels of PD-L1 both in A549 and H1650 cells (P < 0.05). Taken together, our data suggest that miR-155-5p may suppress the expression of PD-L1 in LUAD.
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Project description:AimsAtrial natriuretic peptide (ANP), secreted primarily by atrial cardiomyocytes, decreases blood pressure by raising cyclic 3',5'-guanosine monophosphate (cGMP) levels and inducing vasorelaxation, natriuresis, and diuresis. Raising the level of ANP has been shown to be an effective treatment for hypertension. To advance the future development of an anti-microRNA (miR) approach to increasing expression of ANP, we investigated the regulation of NPPA expression by two miRs: miR-425 and miR-155. We examined whether miR-425 and miR-155 have an additive effect on the expression and function of ANP.Methods and resultsHuman embryonic stem cell-derived cardiomyocytes (hESC-CMs) were transfected with miR-425, miR-155, or a combination of the two miRs. Two days later, NPPA expression was measured using real time qPCR. Each of the miRs decreased NPPA expression over a wide range of concentrations, with a significant reduction at concentrations as low as 1 nM. The combination of miR-425 and miR-155 reduced NPPA expression to a greater extent than either miR-425 or miR-155 alone. An in vitro assay was developed to study the potential biological significance of the miR-induced decrease in NPPA expression. The cooperative effect of miR-425 and miR-155 on NPPA expression was associated with a significant decrease in cGMP levels.ConclusionsThese data demonstrate that miR-425 and miR-155 regulate NPPA expression in a cooperative manner. Targeting both miRNAs with anti-miRs (possibly at submaximal concentrations) might prove to be a more effective strategy to modulate ANP levels, and thus blood pressure, than targeting either miRNA alone.
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Project description:Innate lymphoid cells are a heterogeneous subset of lymphocytes deeply implicated in the innate immune responses to different pathogens, in lymphoid organogenesis and in the maintenance of tissue homeostasis. Group 3 innate lymphoid cells (ILC3) have been detected in human decidua, where they play a role in the early inflammatory phase favoring implantation and tissue remodeling as well as in the subsequent regulatory phase preventing fetal rejection and supporting neoangiogenesis. A balance between inflammation and immune tolerance is required to maintain pregnancy, thus maternal immune system must be controlled by finely tuned mechanisms. MicroRNAs (miRNAs) are small non-coding RNAs with important regulatory roles in immune cells, but their function in decidual ILC3 (dILC3) and decidual NK (dNK) cells is still undefined. Here, we examined the miRNome by microarray in these cells during the first trimester of pregnancy and compared with miRNA profiles of peripheral blood NK (pbNK) cells from pregnant women. We show that distinct miRNA profiles could clearly distinguish dILC3 from NK cells. Correlation analyses revealed that dNK and pbNK miRNome profiles are more similar to each other as compared to dILC3. Overall, our data identified specific miRNA signatures distinguishing dILC3, dNK and pbNK cells.
2020-02-28 | GSE140606 | GEO