<p>Cell-free miR-17-5p as a diagnostic biomarker for gastric cancer inhibits dendritic cell maturation</p>

Abstract

Purpose Gastric cancer (GC) patients display aberrant miRNA expression and defective dendritic cell function. However, the role of cancer cell-derived oncomiR in GC detection and dendritic cell (DC) maturation remains largely elusive. Methods Candidate miRNAs were selected by deep sequencing (8 GC plasma samples vs 8 control plasma samples; 8 GC tissues vs 8 adjacent normal gastric tissues) and confirmed by PCR with 164 plasma samples and 72 formalin-fixed paraffin-embedded GC tissue samples. Their diagnostic performance was evaluated by receiver operating characteristic curve. Cy3 fluorescence signals in DCs, exposed to conditioned medium obtained from BGC-823 cells pre-transfected with Cy3-miR-17-5p, were determined by flow cytometry and visualized by confocal microscopy. Functional and phenotypical alterations of DCs were assayed when DCs were transfected with miR-17-5p in vitro. Results Deep sequencing and RT-PCR confirmed that five shared miRNAs were upregulated in plasma and tissue samples of GC patients. Cell-free miR-17-5p was superior to others in GC detection with an area under the curve of 0.82, and correlated with lymphatic metastasis and poor overall survival. GC cell-shuttled miR-17-5p can be delivered to immature DCs, and they significantly inhibited LPS-stimulated phenotypic maturation by diminishing the expression of maturation markers (MHC II, CD80 and CD86 molecules). In line with those alterations in the phenotypic markers, functional experiments demonstrated that miR-17-5p triggered an inhibitory effect on DCs endocytic activity and decreased tumor necrosis factor-α and IL-12 secretion, while enhancing IL-10 production. Mixed lymphocyte reaction showed that miR-17-5p inhibited the T cell stimulating effect of DCs and favored regulatory T cells expansion. Conclusion GC cell-derived miR-17-5p is a potential biomarker for GC detection. Taken up by DCs, miR-17-5p weakened antitumor immune responses via inhibiting the maturation of dendritic cells.

The competitive endogenous RNA regulatory network reveals potential prognostic biomarkers for overall survival in hepatocellular carcinoma

“…MicroRNA‐27a‐3p can regulate tumor cell invasion and migration through dual specificity protein phosphatase 16 . MicroRNA‐17‐5p can exert an antitumor immune response by inhibiting dendritic cells . MicroRNA‐20b‐5p‐mimic can inhibit tumorigenicity of HCT‐116 cells in Balb/c mice .…”

Exploration of Shared Gene Signatures and Molecular Mechanisms Between Periodontitis and Nonalcoholic Fatty Liver Disease

“…We speculated that periodontitis might be affected by miR-125b-5p. Similarly, miR-17-5p and miR-21-5p were reported to play a part in periodontitis and migration of DCs and were predicted to get involved in NAFLD (Du et al, 2016;Kim et al, 2017;Reis et al, 2018;Cui et al, 2019;Zhang et al, 2020;Lin et al, 2022). Although these miRNAs have not been verified in the microenvironment of comorbidity with periodontitis and NAFLD, they also provide important therapeutic targets.…”

Extracellular vesicles cargo from head and neck cancer cell lines disrupt dendritic cells function and match plasma microRNAs

“…Our study identified miRNAs within EVs with essential roles in DC function, a subset of these miRNAs target genes found to be down-regulated in DCs cultivated in the presence of EVs (Table 3 ). In fact, miRNAs have been shown to contribute to the inibition of immune responses when carried by EVs, with effects on monocyte differentiation into macrophages 36 , production of inflammatory cytokines and co-stimulatory molecules by DCs 38 , 39 , antigen processing and presentation 41 , MHC II molecules expression 29 , 49 , DC maturation 44 , 52 , migration 47 , and increased DC death 51 . Additionally, these miRNAs could potentially cooperate to regulate genes involved in these processes since different miRNAs carried by EVs were shown to regulate the same genes: miR-17-5p, miR-21, miR-24 and miR-181 target TNF-a 41 , 44 , 45 , miR-17-5p and miR-24 target IL-12 41 , 44 , and miR-155 and miR-181 regulate IL-1 42 , 60 .…”